14196nas a2204789 4500008004100000022001400041245010000055210006900155260001300224300001100237490000700248520080700255653001601062653002001078653001401098653001601112653002301128653004001151653003801191653003401229653001101263653001201274653003601286100002801322700002301350700002101373700001901394700002501413700002101438700002301459700002501482700001801507700001801525700002301543700002201566700002301588700001101611700003101622700001801653700003201671700002601703700002301729700002101752700002001773700002101793700002201814700002301836700001901859700001801878700001801896700001801914700002301932700002801955700001501983700002501998700001602023700002102039700002102060700002102081700002502102700001902127700002602146700001602172700001902188700001902207700002102226700001602247700001902263700001602282700002202298700002402320700002602344700001902370700002402389700001902413700001802432700002002450700002002470700001602490700002302506700002202529700001902551700002102570700002502591700002002616700002002636700002602656700002202682700002002704700002502724700002302749700002602772700002502798700002202823700002102845700002602866700002302892700002302915700002302938700002402961700002002985700002103005700001703026700002403043700002003067700002603087700001903113700002103132700001903153700002103172700002103193700002603214700002303240700002103263700002403284700001903308700002203327700003003349700001603379700002503395700002503420700002103445700002403466700002003490700002003510700002803530700003503558700002203593700001903615700002103634700001903655700001803674700001803692700001803710700002403728700001603752700001803768700001803786700002003804700002403824700002203848700002303870700002603893700002203919700003003941700002103971700002003992700002304012700001204035700001804047700002104065700001904086700002204105700002304127700001504150700002204165700002104187700002304208700002804231700002704259700002404286700002204310700002804332700002204360700002204382700002204404700002204426700002104448700002804469700002104497700001704518700001904535700001804554700001604572700001604588700002204604700001504626700002104641700001904662700002204681700001704703700002304720700002204743700001604765700002104781700001904802700001904821700002204840700002304862700002004885700002304905700001804928700002004946700002004966700001804986700002205004700001705026700002005043700002005063700002205083700002005105700002205125700002105147700002205168700002205190700001705212700002305229700002305252700002105275700002005296700001905316700001705335700001805352700002405370700002205394700001905416700002205435700002205457700001905479700001705498700002405515700002505539700002105564700002205585700001905607700002005626700001605646700002105662700002005683700003005703700002305733700001605756700001605772700002105788700002005809700001905829700001905848700002705867700002205894700001905916700001805935700002005953700002005973700002105993700002606014700001906040700001906059700002306078700001806101700002006119700002106139700002506160700001806185700002006203700002606223700002006249700001906269700002206288700002406310700002006334700001906354700002406373700001706397700002006414700001606434700002306450700001706473700001806490700002406508700002406532700002406556700002406580700002206604700001906626700001806645700002206663700002606685700002406711700001906735700001906754700002706773700002206800700002206822700002406844700002206868700002506890700002206915700002106937700002106958700001906979700002306998700002107021700002807042700001707070700001907087700001607106700002107122700001907143700002007162700001907182700002407201700002307225700001907248700002007267700002507287700002107312700002407333700001907357700002007376700002007396700002207416700002507438700001907463700002107482700002307503700002307526700002407549700002407573700002507597700002407622700002207646700002207668700002207690700002007712700001407732700001907746700002207765700002607787700002207813700002207835700001707857700002007874700001807894700002707912700001907939700001907958700001807977700002707995700001708022700001908039700002208058700002108080700002408101700002408125700001908149700002308168700002008191700002608211700002408237700002008261700001908281700001608300700002208316700002408338700002308362700002408385700002308409700001708432700002408449700001908473700002108492700002008513700002508533700001808558700002108576700002008597700002508617700002508642700002508667700001908692700002008711700002308731700002908754700002308783700002008806700002108826700001908847700002308866700002108889700002208910700002108932700002608953700002008979700002408999700002309023700002309046700002209069700002509091700002809116700002509144700001909169700002109188700002109209700001909230700002209249700002409271700002009295700002009315710001009335710002509345856003609370 2010 eng d a1546-171800aAssociation analyses of 249,796 individuals reveal 18 new loci associated with body mass index.0 aAssociation analyses of 249796 individuals reveal 18 new loci as c2010 Nov a937-480 v423 a
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
10aBody Height10aBody Mass Index10aBody Size10aBody Weight10aChromosome Mapping10aEuropean Continental Ancestry Group10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aObesity10aPolymorphism, Single Nucleotide1 aSpeliotes, Elizabeth, K1 aWiller, Cristen, J1 aBerndt, Sonja, I1 aMonda, Keri, L1 aThorleifsson, Gudmar1 aJackson, Anne, U1 aAllen, Hana, Lango1 aLindgren, Cecilia, M1 aLuan, Jian'an1 aMägi, Reedik1 aRandall, Joshua, C1 aVedantam, Sailaja1 aWinkler, Thomas, W1 aQi, Lu1 aWorkalemahu, Tsegaselassie1 aHeid, Iris, M1 aSteinthorsdottir, Valgerdur1 aStringham, Heather, M1 aWeedon, Michael, N1 aWheeler, Eleanor1 aWood, Andrew, R1 aFerreira, Teresa1 aWeyant, Robert, J1 aSegrè, Ayellet, V1 aEstrada, Karol1 aLiang, Liming1 aNemesh, James1 aPark, Ju-Hyun1 aGustafsson, Stefan1 aKilpeläinen, Tuomas, O1 aYang, Jian1 aBouatia-Naji, Nabila1 aEsko, Tõnu1 aFeitosa, Mary, F1 aKutalik, Zoltán1 aMangino, Massimo1 aRaychaudhuri, Soumya1 aScherag, Andre1 aSmith, Albert, Vernon1 aWelch, Ryan1 aZhao, Jing Hua1 aAben, Katja, K1 aAbsher, Devin, M1 aAmin, Najaf1 aDixon, Anna, L1 aFisher, Eva1 aGlazer, Nicole, L1 aGoddard, Michael, E1 aHeard-Costa, Nancy, L1 aHoesel, Volker1 aHottenga, Jouke-Jan1 aJohansson, Asa1 aJohnson, Toby1 aKetkar, Shamika1 aLamina, Claudia1 aLi, Shengxu1 aMoffatt, Miriam, F1 aMyers, Richard, H1 aNarisu, Narisu1 aPerry, John, R B1 aPeters, Marjolein, J1 aPreuss, Michael1 aRipatti, Samuli1 aRivadeneira, Fernando1 aSandholt, Camilla1 aScott, Laura, J1 aTimpson, Nicholas, J1 aTyrer, Jonathan, P1 avan Wingerden, Sophie1 aWatanabe, Richard, M1 aWhite, Charles, C1 aWiklund, Fredrik1 aBarlassina, Christina1 aChasman, Daniel, I1 aCooper, Matthew, N1 aJansson, John-Olov1 aLawrence, Robert, W1 aPellikka, Niina1 aProkopenko, Inga1 aShi, Jianxin1 aThiering, Elisabeth1 aAlavere, Helene1 aAlibrandi, Maria, T S1 aAlmgren, Peter1 aArnold, Alice, M1 aAspelund, Thor1 aAtwood, Larry, D1 aBalkau, Beverley1 aBalmforth, Anthony, J1 aBennett, Amanda, J1 aBen-Shlomo, Yoav1 aBergman, Richard, N1 aBergmann, Sven1 aBiebermann, Heike1 aBlakemore, Alexandra, I F1 aBoes, Tanja1 aBonnycastle, Lori, L1 aBornstein, Stefan, R1 aBrown, Morris, J1 aBuchanan, Thomas, A1 aBusonero, Fabio1 aCampbell, Harry1 aCappuccio, Francesco, P1 aCavalcanti-Proença, Christine1 aChen, Yii-Der Ida1 aChen, Chih-Mei1 aChines, Peter, S1 aClarke, Robert1 aCoin, Lachlan1 aConnell, John1 aDay, Ian, N M1 aHeijer, Martin, den1 aDuan, Jubao1 aEbrahim, Shah1 aElliott, Paul1 aElosua, Roberto1 aEiriksdottir, Gudny1 aErdos, Michael, R1 aEriksson, Johan, G1 aFacheris, Maurizio, F1 aFelix, Stephan, B1 aFischer-Posovszky, Pamela1 aFolsom, Aaron, R1 aFriedrich, Nele1 aFreimer, Nelson, B1 aFu, Mao1 aGaget, Stefan1 aGejman, Pablo, V1 aGeus, Eco, J C1 aGieger, Christian1 aGjesing, Anette, P1 aGoel, Anuj1 aGoyette, Philippe1 aGrallert, Harald1 aGrässler, Jürgen1 aGreenawalt, Danielle, M1 aGroves, Christopher, J1 aGudnason, Vilmundur1 aGuiducci, Candace1 aHartikainen, Anna-Liisa1 aHassanali, Neelam1 aHall, Alistair, S1 aHavulinna, Aki, S1 aHayward, Caroline1 aHeath, Andrew, C1 aHengstenberg, Christian1 aHicks, Andrew, A1 aHinney, Anke1 aHofman, Albert1 aHomuth, Georg1 aHui, Jennie1 aIgl, Wilmar1 aIribarren, Carlos1 aIsomaa, Bo1 aJacobs, Kevin, B1 aJarick, Ivonne1 aJewell, Elizabeth1 aJohn, Ulrich1 aJørgensen, Torben1 aJousilahti, Pekka1 aJula, Antti1 aKaakinen, Marika1 aKajantie, Eero1 aKaplan, Lee, M1 aKathiresan, Sekar1 aKettunen, Johannes1 aKinnunen, Leena1 aKnowles, Joshua, W1 aKolcic, Ivana1 aKönig, Inke, R1 aKoskinen, Seppo1 aKovacs, Peter1 aKuusisto, Johanna1 aKraft, Peter1 aKvaløy, Kirsti1 aLaitinen, Jaana1 aLantieri, Olivier1 aLanzani, Chiara1 aLauner, Lenore, J1 aLecoeur, Cécile1 aLehtimäki, Terho1 aLettre, Guillaume1 aLiu, Jianjun1 aLokki, Marja-Liisa1 aLorentzon, Mattias1 aLuben, Robert, N1 aLudwig, Barbara1 aManunta, Paolo1 aMarek, Diana1 aMarre, Michel1 aMartin, Nicholas, G1 aMcArdle, Wendy, L1 aMcCarthy, Anne1 aMcKnight, Barbara1 aMeitinger, Thomas1 aMelander, Olle1 aMeyre, David1 aMidthjell, Kristian1 aMontgomery, Grant, W1 aMorken, Mario, A1 aMorris, Andrew, P1 aMulic, Rosanda1 aNgwa, Julius, S1 aNelis, Mari1 aNeville, Matt, J1 aNyholt, Dale, R1 aO'Donnell, Christopher, J1 aO'Rahilly, Stephen1 aOng, Ken, K1 aOostra, Ben1 aParé, Guillaume1 aParker, Alex, N1 aPerola, Markus1 aPichler, Irene1 aPietiläinen, Kirsi, H1 aPlatou, Carl, G P1 aPolasek, Ozren1 aPouta, Anneli1 aRafelt, Suzanne1 aRaitakari, Olli1 aRayner, Nigel, W1 aRidderstråle, Martin1 aRief, Winfried1 aRuokonen, Aimo1 aRobertson, Neil, R1 aRzehak, Peter1 aSalomaa, Veikko1 aSanders, Alan, R1 aSandhu, Manjinder, S1 aSanna, Serena1 aSaramies, Jouko1 aSavolainen, Markku, J1 aScherag, Susann1 aSchipf, Sabine1 aSchreiber, Stefan1 aSchunkert, Heribert1 aSilander, Kaisa1 aSinisalo, Juha1 aSiscovick, David, S1 aSmit, Jan, H1 aSoranzo, Nicole1 aSovio, Ulla1 aStephens, Jonathan1 aSurakka, Ida1 aSwift, Amy, J1 aTammesoo, Mari-Liis1 aTardif, Jean-Claude1 aTeder-Laving, Maris1 aTeslovich, Tanya, M1 aThompson, John, R1 aThomson, Brian1 aTönjes, Anke1 aTuomi, Tiinamaija1 avan Meurs, Joyce, B J1 avan Ommen, Gert-Jan1 aVatin, Vincent1 aViikari, Jorma1 aVisvikis-Siest, Sophie1 aVitart, Veronique1 aVogel, Carla, I G1 aVoight, Benjamin, F1 aWaite, Lindsay, L1 aWallaschofski, Henri1 aWalters, Bragi, G1 aWiden, Elisabeth1 aWiegand, Susanna1 aWild, Sarah, H1 aWillemsen, Gonneke1 aWitte, Daniel, R1 aWitteman, Jacqueline, C1 aXu, Jianfeng1 aZhang, Qunyuan1 aZgaga, Lina1 aZiegler, Andreas1 aZitting, Paavo1 aBeilby, John, P1 aFarooqi, Sadaf1 aHebebrand, Johannes1 aHuikuri, Heikki, V1 aJames, Alan, L1 aKähönen, Mika1 aLevinson, Douglas, F1 aMacciardi, Fabio1 aNieminen, Markku, S1 aOhlsson, Claes1 aPalmer, Lyle, J1 aRidker, Paul, M1 aStumvoll, Michael1 aBeckmann, Jacques, S1 aBoeing, Heiner1 aBoerwinkle, Eric1 aBoomsma, Dorret, I1 aCaulfield, Mark, J1 aChanock, Stephen, J1 aCollins, Francis, S1 aCupples, Adrienne, L1 aSmith, George Davey1 aErdmann, Jeanette1 aFroguel, Philippe1 aGrönberg, Henrik1 aGyllensten, Ulf1 aHall, Per1 aHansen, Torben1 aHarris, Tamara, B1 aHattersley, Andrew, T1 aHayes, Richard, B1 aHeinrich, Joachim1 aHu, Frank, B1 aHveem, Kristian1 aIllig, Thomas1 aJarvelin, Marjo-Riitta1 aKaprio, Jaakko1 aKarpe, Fredrik1 aKhaw, Kay-Tee1 aKiemeney, Lambertus, A1 aKrude, Heiko1 aLaakso, Markku1 aLawlor, Debbie, A1 aMetspalu, Andres1 aMunroe, Patricia, B1 aOuwehand, Willem, H1 aPedersen, Oluf1 aPenninx, Brenda, W1 aPeters, Annette1 aPramstaller, Peter, P1 aQuertermous, Thomas1 aReinehr, Thomas1 aRissanen, Aila1 aRudan, Igor1 aSamani, Nilesh, J1 aSchwarz, Peter, E H1 aShuldiner, Alan, R1 aSpector, Timothy, D1 aTuomilehto, Jaakko1 aUda, Manuela1 aUitterlinden, Andre1 aValle, Timo, T1 aWabitsch, Martin1 aWaeber, Gérard1 aWareham, Nicholas, J1 aWatkins, Hugh1 aWilson, James, F1 aWright, Alan, F1 aZillikens, Carola, M1 aChatterjee, Nilanjan1 aMcCarroll, Steven, A1 aPurcell, Shaun1 aSchadt, Eric, E1 aVisscher, Peter, M1 aAssimes, Themistocles, L1 aBorecki, Ingrid, B1 aDeloukas, Panos1 aFox, Caroline, S1 aGroop, Leif, C1 aHaritunians, Talin1 aHunter, David, J1 aKaplan, Robert, C1 aMohlke, Karen, L1 aO'Connell, Jeffrey, R1 aPeltonen, Leena1 aSchlessinger, David1 aStrachan, David, P1 aDuijn, Cornelia, M1 aWichmann, H-Erich1 aFrayling, Timothy, M1 aThorsteinsdottir, Unnur1 aAbecasis, Goncalo, R1 aBarroso, Inês1 aBoehnke, Michael1 aStefansson, Kari1 aNorth, Kari, E1 aMcCarthy, Mark, I1 aHirschhorn, Joel, N1 aIngelsson, Erik1 aLoos, Ruth, J F1 aMAGIC1 aProcardis Consortium uhttps://chs-nhlbi.org/node/123704709nas a2201405 4500008004100000022001400041245010700055210006900162260001300231300001200244490000700256520077800263653002601041653001801067653002001085653001701105653003801122653002201160653001801182653003401200653001101234653003101245100001801276700002601294700002401320700001401344700002901358700001701387700002101404700002101425700001501446700002101461700002201482700001901504700002301523700002201546700002401568700002001592700001601612700002301628700001801651700001801669700002701687700002501714700002501739700002501764700002201789700001901811700002001830700001901850700002001869700002001889700002001909700002601929700002001955700002501975700001902000700002102019700001802040700002902058700001902087700002002106700001602126700002002142700001902162700002002181700002102201700001602222700002302238700002002261700001802281700002202299700002402321700002202345700002302367700002302390700001702413700001902430700001802449700001702467700001702484700002202501700001902523700001702542700002002559700002002579700001902599700002402618700002102642700002102663700002002684700002202704700001702726700001902743700002302762700002602785700002002811700002402831700001802855700002002873700002302893700002102916700001902937700001902956700002202975700002202997700002303019700002303042700002303065700002203088700002403110700001903134700002203153700001703175700001703192700002203209700001803231700001803249856003603267 2010 eng d a1546-171800aGenome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.0 aGenomewide metaanalysis increases to 71 the number of confirmed c2010 Dec a1118-250 v423 aWe undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
10aComputational Biology10aCrohn Disease10aGenetic Linkage10aGenetic Loci10aGenetic Predisposition to Disease10aGenetic Variation10aGenome, Human10aGenome-Wide Association Study10aHumans10aReproducibility of Results1 aFranke, Andre1 aMcGovern, Dermot, P B1 aBarrett, Jeffrey, C1 aWang, Kai1 aRadford-Smith, Graham, L1 aAhmad, Tariq1 aLees, Charlie, W1 aBalschun, Tobias1 aLee, James1 aRoberts, Rebecca1 aAnderson, Carl, A1 aBis, Joshua, C1 aBumpstead, Suzanne1 aEllinghaus, David1 aFesten, Eleonora, M1 aGeorges, Michel1 aGreen, Todd1 aHaritunians, Talin1 aJostins, Luke1 aLatiano, Anna1 aMathew, Christopher, G1 aMontgomery, Grant, W1 aPrescott, Natalie, J1 aRaychaudhuri, Soumya1 aRotter, Jerome, I1 aSchumm, Philip1 aSharma, Yashoda1 aSimms, Lisa, A1 aTaylor, Kent, D1 aWhiteman, David1 aWijmenga, Cisca1 aBaldassano, Robert, N1 aBarclay, Murray1 aBayless, Theodore, M1 aBrand, Stephan1 aBüning, Carsten1 aCohen, Albert1 aColombel, Jean-Frederick1 aCottone, Mario1 aStronati, Laura1 aDenson, Ted1 aDe Vos, Martine1 aD'Inca, Renata1 aDubinsky, Marla1 aEdwards, Cathryn1 aFlorin, Tim1 aFranchimont, Denis1 aGearry, Richard1 aGlas, Jürgen1 aVan Gossum, Andre1 aGuthery, Stephen, L1 aHalfvarson, Jonas1 aVerspaget, Hein, W1 aHugot, Jean-Pierre1 aKarban, Amir1 aLaukens, Debby1 aLawrance, Ian1 aLemann, Marc1 aLevine, Arie1 aLibioulle, Cecile1 aLouis, Edouard1 aMowat, Craig1 aNewman, William1 aPanés, Julián1 aPhillips, Anne1 aProctor, Deborah, D1 aRegueiro, Miguel1 aRussell, Richard1 aRutgeerts, Paul1 aSanderson, Jeremy1 aSans, Miquel1 aSeibold, Frank1 aSteinhart, Hillary1 aStokkers, Pieter, C F1 aTörkvist, Leif1 aKullak-Ublick, Gerd1 aWilson, David1 aWalters, Thomas1 aTargan, Stephan, R1 aBrant, Steven, R1 aRioux, John, D1 aD'Amato, Mauro1 aWeersma, Rinse, K1 aKugathasan, Subra1 aGriffiths, Anne, M1 aMansfield, John, C1 aVermeire, Severine1 aDuerr, Richard, H1 aSilverberg, Mark, S1 aSatsangi, Jack1 aSchreiber, Stefan1 aCho, Judy, H1 aAnnese, Vito1 aHakonarson, Hakon1 aDaly, Mark, J1 aParkes, Miles uhttps://chs-nhlbi.org/node/124912698nas a2203781 4500008004100000022001400041245009600055210006900151260001600220300001000236490000800246520210000254653001602354653003102370653001702401653003802418653001802456653003402474653001102508653003602519653003102555653001402586653003602600100002302636700001902659700002202678700002102700700002302721700002602744700002302770700002102793700002202814700002502836700002102861700002002882700002202902700002302924700002802947700002102975700002002996700001803016700001503034700002503049700002603074700002303100700001103123700002603134700001803160700001903178700001803197700001803215700001803233700002503251700002303276700002403299700001703323700002003340700003103360700002403391700001903415700002503434700002103459700001603480700001803496700002003514700001703534700002103551700002103572700001803593700001803611700001903629700002203648700002203670700002403692700002103716700002303737700002103760700001903781700001903800700002003819700002103839700002303860700003203883700002303915700002403938700002103962700001703983700001904000700002004019700002004039700001904059700002104078700001704099700002404116700002704140700001604167700001904183700002104202700002304223700002304246700002004269700001804289700002304307700001904330700001904349700002004368700001204388700002104400700001904421700002304440700002004463700001504483700002404498700002504522700002304547700002204570700002204592700002104614700002204635700001904657700002004676700001904696700001704715700001804732700001704750700001604767700002204783700002404805700002404829700002604853700002204879700002204901700002104923700001904944700002604963700002004989700002105009700002605030700002105056700001605077700001805093700002005111700002305131700002305154700001905177700002105196700001805217700002805235700002205263700002105285700001605306700001605322700001805338700001605356700001905372700002805391700002105419700001805440700002005458700001805478700002005496700001705516700002305533700001705556700002005573700002205593700002105615700002105636700002005657700001905677700002305696700001905719700002705738700001805765700002605783700002205809700002605831700002105857700002905878700001905907700001705926700002605943700001905969700002105988700001906009700002306028700001806051700001606069700001906085700002006104700002006124700002206144700001606166700002506182700002006207700002606227700001906253700002306272700002506295700002006320700002406340700001906364700002406383700001806407700002406425700002406449700002106473700002206494700002006516700002306536700002206559700002006581700001906601700002206620700002406642700001906666700002206685700002206707700001906729700001906748700002006767700002406787700003006811700001906841700001606860700002006876700002006896700002006916700001906936700001906955700001906974700002406993700002307017700002407040700002207064700001807086700002307104700002407127700001907151700002107170700002407191700002507215700002507240700002007265700002107285700002107306700002107327700002407348700002007372700002207392700002207414700001407436700002607450700002807476700002207504700002107526700002007547700002207567700001707589700002107606700002007627700002907647700001907676700001907695700002107714700002307735700002307758700002507781700002207806700002107828700002407849700002007873700002207893700002207915700002707937700002007964700002407984700002408008700002308032700002608055700002408081700001608105700002208121700002408143700001908167700001808186700002108204700001908225700002308244700001708267700002208284700002108306700001908327700002408346700002508370700002108395700002608416700002308442700002208465700002308487700002308510700002008533700002808553700002008581700002808601700002308629700002508652700002008677700002108697700002208718700002008740700002508760700002508785700002108810700002508831700002408856856003608880 2010 eng d a1476-468700aHundreds of variants clustered in genomic loci and biological pathways affect human height.0 aHundreds of variants clustered in genomic loci and biological pa c2010 Oct 14 a832-80 v4673 aMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
10aBody Height10aChromosomes, Human, Pair 310aGenetic Loci10aGenetic Predisposition to Disease10aGenome, Human10aGenome-Wide Association Study10aHumans10aMetabolic Networks and Pathways10aMultifactorial Inheritance10aPhenotype10aPolymorphism, Single Nucleotide1 aAllen, Hana, Lango1 aEstrada, Karol1 aLettre, Guillaume1 aBerndt, Sonja, I1 aWeedon, Michael, N1 aRivadeneira, Fernando1 aWiller, Cristen, J1 aJackson, Anne, U1 aVedantam, Sailaja1 aRaychaudhuri, Soumya1 aFerreira, Teresa1 aWood, Andrew, R1 aWeyant, Robert, J1 aSegrè, Ayellet, V1 aSpeliotes, Elizabeth, K1 aWheeler, Eleanor1 aSoranzo, Nicole1 aPark, Ju-Hyun1 aYang, Jian1 aGudbjartsson, Daniel1 aHeard-Costa, Nancy, L1 aRandall, Joshua, C1 aQi, Lu1 aSmith, Albert, Vernon1 aMägi, Reedik1 aPastinen, Tomi1 aLiang, Liming1 aHeid, Iris, M1 aLuan, Jian'an1 aThorleifsson, Gudmar1 aWinkler, Thomas, W1 aGoddard, Michael, E1 aLo, Ken, Sin1 aPalmer, Cameron1 aWorkalemahu, Tsegaselassie1 aAulchenko, Yurii, S1 aJohansson, Asa1 aZillikens, Carola, M1 aFeitosa, Mary, F1 aEsko, Tõnu1 aJohnson, Toby1 aKetkar, Shamika1 aKraft, Peter1 aMangino, Massimo1 aProkopenko, Inga1 aAbsher, Devin1 aAlbrecht, Eva1 aErnst, Florian1 aGlazer, Nicole, L1 aHayward, Caroline1 aHottenga, Jouke-Jan1 aJacobs, Kevin, B1 aKnowles, Joshua, W1 aKutalik, Zoltán1 aMonda, Keri, L1 aPolasek, Ozren1 aPreuss, Michael1 aRayner, Nigel, W1 aRobertson, Neil, R1 aSteinthorsdottir, Valgerdur1 aTyrer, Jonathan, P1 aVoight, Benjamin, F1 aWiklund, Fredrik1 aXu, Jianfeng1 aZhao, Jing Hua1 aNyholt, Dale, R1 aPellikka, Niina1 aPerola, Markus1 aPerry, John, R B1 aSurakka, Ida1 aTammesoo, Mari-Liis1 aAltmaier, Elizabeth, L1 aAmin, Najaf1 aAspelund, Thor1 aBhangale, Tushar1 aBoucher, Gabrielle1 aChasman, Daniel, I1 aChen, Constance1 aCoin, Lachlan1 aCooper, Matthew, N1 aDixon, Anna, L1 aGibson, Quince1 aGrundberg, Elin1 aHao, Ke1 aJunttila, Juhani1 aKaplan, Lee, M1 aKettunen, Johannes1 aKönig, Inke, R1 aKwan, Tony1 aLawrence, Robert, W1 aLevinson, Douglas, F1 aLorentzon, Mattias1 aMcKnight, Barbara1 aMorris, Andrew, P1 aMüller, Martina1 aNgwa, Julius, Suh1 aPurcell, Shaun1 aRafelt, Suzanne1 aSalem, Rany, M1 aSalvi, Erika1 aSanna, Serena1 aShi, Jianxin1 aSovio, Ulla1 aThompson, John, R1 aTurchin, Michael, C1 aVandenput, Liesbeth1 aVerlaan, Dominique, J1 aVitart, Veronique1 aWhite, Charles, C1 aZiegler, Andreas1 aAlmgren, Peter1 aBalmforth, Anthony, J1 aCampbell, Harry1 aCitterio, Lorena1 aDe Grandi, Alessandro1 aDominiczak, Anna1 aDuan, Jubao1 aElliott, Paul1 aElosua, Roberto1 aEriksson, Johan, G1 aFreimer, Nelson, B1 aGeus, Eco, J C1 aGlorioso, Nicola1 aHaiqing, Shen1 aHartikainen, Anna-Liisa1 aHavulinna, Aki, S1 aHicks, Andrew, A1 aHui, Jennie1 aIgl, Wilmar1 aIllig, Thomas1 aJula, Antti1 aKajantie, Eero1 aKilpeläinen, Tuomas, O1 aKoiranen, Markku1 aKolcic, Ivana1 aKoskinen, Seppo1 aKovacs, Peter1 aLaitinen, Jaana1 aLiu, Jianjun1 aLokki, Marja-Liisa1 aMarusic, Ana1 aMaschio, Andrea1 aMeitinger, Thomas1 aMulas, Antonella1 aParé, Guillaume1 aParker, Alex, N1 aPeden, John, F1 aPetersmann, Astrid1 aPichler, Irene1 aPietiläinen, Kirsi, H1 aPouta, Anneli1 aRidderstråle, Martin1 aRotter, Jerome, I1 aSambrook, Jennifer, G1 aSanders, Alan, R1 aSchmidt, Carsten, Oliver1 aSinisalo, Juha1 aSmit, Jan, H1 aStringham, Heather, M1 aWalters, Bragi1 aWiden, Elisabeth1 aWild, Sarah, H1 aWillemsen, Gonneke1 aZagato, Laura1 aZgaga, Lina1 aZitting, Paavo1 aAlavere, Helene1 aFarrall, Martin1 aMcArdle, Wendy, L1 aNelis, Mari1 aPeters, Marjolein, J1 aRipatti, Samuli1 avan Meurs, Joyce, B J1 aAben, Katja, K1 aArdlie, Kristin, G1 aBeckmann, Jacques, S1 aBeilby, John, P1 aBergman, Richard, N1 aBergmann, Sven1 aCollins, Francis, S1 aCusi, Daniele1 aHeijer, Martin, den1 aEiriksdottir, Gudny1 aGejman, Pablo, V1 aHall, Alistair, S1 aHamsten, Anders1 aHuikuri, Heikki, V1 aIribarren, Carlos1 aKähönen, Mika1 aKaprio, Jaakko1 aKathiresan, Sekar1 aKiemeney, Lambertus1 aKocher, Thomas1 aLauner, Lenore, J1 aLehtimäki, Terho1 aMelander, Olle1 aMosley, Tom, H1 aMusk, Arthur, W1 aNieminen, Markku, S1 aO'Donnell, Christopher, J1 aOhlsson, Claes1 aOostra, Ben1 aPalmer, Lyle, J1 aRaitakari, Olli1 aRidker, Paul, M1 aRioux, John, D1 aRissanen, Aila1 aRivolta, Carlo1 aSchunkert, Heribert1 aShuldiner, Alan, R1 aSiscovick, David, S1 aStumvoll, Michael1 aTönjes, Anke1 aTuomilehto, Jaakko1 avan Ommen, Gert-Jan1 aViikari, Jorma1 aHeath, Andrew, C1 aMartin, Nicholas, G1 aMontgomery, Grant, W1 aProvince, Michael, A1 aKayser, Manfred1 aArnold, Alice, M1 aAtwood, Larry, D1 aBoerwinkle, Eric1 aChanock, Stephen, J1 aDeloukas, Panos1 aGieger, Christian1 aGrönberg, Henrik1 aHall, Per1 aHattersley, Andrew, T1 aHengstenberg, Christian1 aHoffman, Wolfgang1 aLathrop, Mark, G1 aSalomaa, Veikko1 aSchreiber, Stefan1 aUda, Manuela1 aWaterworth, Dawn1 aWright, Alan, F1 aAssimes, Themistocles, L1 aBarroso, Inês1 aHofman, Albert1 aMohlke, Karen, L1 aBoomsma, Dorret, I1 aCaulfield, Mark, J1 aCupples, Adrienne, L1 aErdmann, Jeanette1 aFox, Caroline, S1 aGudnason, Vilmundur1 aGyllensten, Ulf1 aHarris, Tamara, B1 aHayes, Richard, B1 aJarvelin, Marjo-Riitta1 aMooser, Vincent1 aMunroe, Patricia, B1 aOuwehand, Willem, H1 aPenninx, Brenda, W1 aPramstaller, Peter, P1 aQuertermous, Thomas1 aRudan, Igor1 aSamani, Nilesh, J1 aSpector, Timothy, D1 aVölzke, Henry1 aWatkins, Hugh1 aWilson, James, F1 aGroop, Leif, C1 aHaritunians, Talin1 aHu, Frank, B1 aKaplan, Robert, C1 aMetspalu, Andres1 aNorth, Kari, E1 aSchlessinger, David1 aWareham, Nicholas, J1 aHunter, David, J1 aO'Connell, Jeffrey, R1 aStrachan, David, P1 aWichmann, H-Erich1 aBorecki, Ingrid, B1 aDuijn, Cornelia, M1 aSchadt, Eric, E1 aThorsteinsdottir, Unnur1 aPeltonen, Leena1 aUitterlinden, André, G1 aVisscher, Peter, M1 aChatterjee, Nilanjan1 aLoos, Ruth, J F1 aBoehnke, Michael1 aMcCarthy, Mark, I1 aIngelsson, Erik1 aLindgren, Cecilia, M1 aAbecasis, Goncalo, R1 aStefansson, Kari1 aFrayling, Timothy, M1 aHirschhorn, Joel, N uhttps://chs-nhlbi.org/node/123408678nas a2202593 4500008004100000022001400041245012400055210006900179260001600248300001200264490000700276520126400283653001701547653002601564653004001590653003401630653001101664653001501675653002001690653003001710653003801740653003401778653001301812653001801825653001101843653005001854653005501904653002101959653000901980653004601989653001702035653002002052653003602072653002802108653001702136653001302153100001902166700002602185700002502211700001902236700002002255700002502275700001402300700002302314700001602337700001802353700002202371700001202393700001802405700002102423700002202444700002402466700001802490700001702508700003102525700002002556700001802576700001902594700002502613700002402638700001702662700002502679700002102704700002102725700001702746700001702763700002202780700001902802700002602821700001802847700002102865700002002886700002802906700001902934700002102953700002202974700002502996700002203021700002103043700001703064700002403081700002303105700001703128700002203145700002303167700002003190700001903210700002103229700001603250700002603266700002003292700001903312700002103331700001903352700001903371700002003390700002803410700002103438700001903459700002003478700002003498700002703518700001403545700001303559700002103572700002503593700002403618700001703642700002403659700001803683700002203701700001403723700001803737700002003755700003003775700002003805700002103825700002403846700001803870700002203888700002903910700002303939700001503962700002103977700002103998700001604019700002004035700003104055700002004086700003004106700001904136700002204155700002004177700002404197700002004221700002204241700002004263700001704283700001904300700002704319700002404346700003104370700002004401700002104421700002704442700002604469700001504495700001204510700001804522700002804540700002404568700001604592700002204608700002304630700002604653700002304679700002704702700002004729700001704749700002204766700001904788700002504807700002004832700002304852700002104875700002404896700001904920700002404939700002104963700002004984700002405004700001905028700002405047700001805071700001905089700001805108700002205126700001705148700002305165700002205188700002505210700002705235700002705262700001905289700001905308700002305327700002305350700002005373700001705393700001805410700002405428700002105452700002305473700002505496700002305521700002105544700002505565700002205590700002005612700002205632700002605654700002005680700002005700700002405720700002705744700002505771700002805796700001905824700001905843700002005862700002205882700002105904700002805925700002305953700002505976700002106001700002606022856003606048 2012 eng d a1546-171800aGenome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.0 aGenomewide metaanalysis identifies 56 bone mineral density loci c2012 Apr 15 a491-5010 v443 aBone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
10aBone Density10aComputational Biology10aEuropean Continental Ancestry Group10aExtracellular Matrix Proteins10aFemale10aFemur Neck10aFractures, Bone10aGene Expression Profiling10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aGlycoproteins10aHumans10aIntercellular Signaling Peptides and Proteins10aLow Density Lipoprotein Receptor-Related Protein-510aLumbar Vertebrae10aMale10aMitochondrial Membrane Transport Proteins10aOsteoporosis10aPhosphoproteins10aPolymorphism, Single Nucleotide10aQuantitative Trait Loci10aRisk Factors10aSpectrin1 aEstrada, Karol1 aStyrkarsdottir, Unnur1 aEvangelou, Evangelos1 aHsu, Yi-Hsiang1 aDuncan, Emma, L1 aNtzani, Evangelia, E1 aOei, Ling1 aAlbagha, Omar, M E1 aAmin, Najaf1 aKemp, John, P1 aKoller, Daniel, L1 aLi, Guo1 aLiu, Ching-Ti1 aMinster, Ryan, L1 aMoayyeri, Alireza1 aVandenput, Liesbeth1 aWillner, Dana1 aXiao, Su-Mei1 aYerges-Armstrong, Laura, M1 aZheng, Hou-Feng1 aAlonso, Nerea1 aEriksson, Joel1 aKammerer, Candace, M1 aKaptoge, Stephen, K1 aLeo, Paul, J1 aThorleifsson, Gudmar1 aWilson, Scott, G1 aWilson, James, F1 aAalto, Ville1 aAlen, Markku1 aAragaki, Aaron, K1 aAspelund, Thor1 aCenter, Jacqueline, R1 aDailiana, Zoe1 aDuggan, David, J1 aGarcia, Melissa1 aGarcía-Giralt, Natalia1 aGiroux, Sylvie1 aHallmans, Göran1 aHocking, Lynne, J1 aHusted, Lise, Bjerre1 aJameson, Karen, A1 aKhusainova, Rita1 aKim, Ghi, Su1 aKooperberg, Charles1 aKoromila, Theodora1 aKruk, Marcin1 aLaaksonen, Marika1 aLaCroix, Andrea, Z1 aLee, Seung, Hun1 aLeung, Ping, C1 aLewis, Joshua, R1 aMasi, Laura1 aMencej-Bedrac, Simona1 aNguyen, Tuan, V1 aNogues, Xavier1 aPatel, Millan, S1 aPrezelj, Janez1 aRose, Lynda, M1 aScollen, Serena1 aSiggeirsdottir, Kristin1 aSmith, Albert, V1 aSvensson, Olle1 aTrompet, Stella1 aTrummer, Olivia1 avan Schoor, Natasja, M1 aWoo, Jean1 aZhu, Kun1 aBalcells, Susana1 aBrandi, Maria, Luisa1 aBuckley, Brendan, M1 aCheng, Sulin1 aChristiansen, Claus1 aCooper, Cyrus1 aDedoussis, George1 aFord, Ian1 aFrost, Morten1 aGoltzman, David1 aGonzález-Macías, Jesús1 aKähönen, Mika1 aKarlsson, Magnus1 aKhusnutdinova, Elza1 aKoh, Jung-Min1 aKollia, Panagoula1 aLangdahl, Bente, Lomholt1 aLeslie, William, D1 aLips, Paul1 aLjunggren, Osten1 aLorenc, Roman, S1 aMarc, Janja1 aMellström, Dan1 aObermayer-Pietsch, Barbara1 aOlmos, José, M1 aPettersson-Kymmer, Ulrika1 aReid, David, M1 aRiancho, José, A1 aRidker, Paul, M1 aRousseau, François1 aSlagboom, Eline1 aTang, Nelson, L S1 aUrreizti, Roser1 aVan Hul, Wim1 aViikari, Jorma1 aZarrabeitia, María, T1 aAulchenko, Yurii, S1 aCastano-Betancourt, Martha1 aGrundberg, Elin1 aHerrera, Lizbeth1 aIngvarsson, Thorvaldur1 aJohannsdottir, Hrefna1 aKwan, Tony1 aLi, Rui1 aLuben, Robert1 aMedina-Gómez, Carolina1 aPalsson, Stefan, Th1 aReppe, Sjur1 aRotter, Jerome, I1 aSigurdsson, Gunnar1 avan Meurs, Joyce, B J1 aVerlaan, Dominique1 aWilliams, Frances, M K1 aWood, Andrew, R1 aZhou, Yanhua1 aGautvik, Kaare, M1 aPastinen, Tomi1 aRaychaudhuri, Soumya1 aCauley, Jane, A1 aChasman, Daniel, I1 aClark, Graeme, R1 aCummings, Steven, R1 aDanoy, Patrick1 aDennison, Elaine, M1 aEastell, Richard1 aEisman, John, A1 aGudnason, Vilmundur1 aHofman, Albert1 aJackson, Rebecca, D1 aJones, Graeme1 aJukema, Wouter1 aKhaw, Kay-Tee1 aLehtimäki, Terho1 aLiu, Yongmei1 aLorentzon, Mattias1 aMcCloskey, Eugene1 aMitchell, Braxton, D1 aNandakumar, Kannabiran1 aNicholson, Geoffrey, C1 aOostra, Ben, A1 aPeacock, Munro1 aPols, Huibert, A P1 aPrince, Richard, L1 aRaitakari, Olli1 aReid, Ian, R1 aRobbins, John1 aSambrook, Philip, N1 aSham, Pak, Chung1 aShuldiner, Alan, R1 aTylavsky, Frances, A1 aDuijn, Cornelia, M1 aWareham, Nick, J1 aCupples, Adrienne, L1 aEcons, Michael, J1 aEvans, David, M1 aHarris, Tamara, B1 aKung, Annie, Wai Chee1 aPsaty, Bruce, M1 aReeve, Jonathan1 aSpector, Timothy, D1 aStreeten, Elizabeth, A1 aZillikens, Carola, M1 aThorsteinsdottir, Unnur1 aOhlsson, Claes1 aKarasik, David1 aRichards, Brent1 aBrown, Matthew, A1 aStefansson, Kari1 aUitterlinden, André, G1 aRalston, Stuart, H1 aIoannidis, John, P A1 aKiel, Douglas, P1 aRivadeneira, Fernando uhttps://chs-nhlbi.org/node/801608958nas a2202881 4500008004100000022001400041245014400055210006900199260001300268300001300281490000700294520091900301653001001220653001201230653001801242653001201260653001101272653001901283653003401302653001101336653001201347653000901359653003601368653000901404653002601413653002801439100002101467700002001488700001901508700002101527700002201548700001801570700001801588700002501606700001901631700002301650700002201673700003101695700001601726700002101742700002001763700001801783700001801801700002301819700001901842700001801861700002001879700001801899700002501917700002401942700001601966700002101982700002002003700002202023700001702045700001902062700002502081700002002106700002302126700001302149700002502162700001602187700002402203700001402227700002202241700001702263700001802280700002602298700002302324700002202347700002202369700001602391700002102407700002002428700001502448700002402463700002502487700001402512700002502526700002202551700002102573700002002594700001702614700001802631700002502649700002102674700002102695700002102716700002002737700002602757700001802783700002002801700001902821700001502840700002102855700001302876700003002889700002802919700002102947700002102968700002002989700002903009700002403038700002103062700001903083700002103102700002003123700001803143700002003161700002103181700001703202700002103219700002203240700002003262700001403282700002503296700002003321700001803341700001903359700002203378700002403400700002003424700001603444700002103460700001803481700001903499700001703518700002003535700001903555700001903574700002603593700002803619700002303647700002103670700002303691700002203714700002003736700001903756700002503775700002003800700002103820700002403841700002203865700001803887700002203905700002203927700002503949700001903974700002303993700002304016700002104039700002004060700002204080700002304102700002004125700002604145700002504171700002304196700002404219700001604243700002004259700001804279700002004297700002204317700002004339700002404359700002404383700002404407700002304431700002504454700001904479700002304498700001904521700001904540700002004559700002404579700002104603700002004624700001804644700002104662700002004683700002704703700002204730700001904752700002104771700002504792700002004817700002004837700001504857700002104872700002304893700002304916700002204939700001804961700002404979700002005003700001905023700002205042700001905064700002505083700002405108700001905132700002105151700002005172700002405192700002005216700001805236700001805254700002005272700002405292700001905316700002105335700003705356700002205393700002305415700002105438700001505459700001905474700002305493700001905516700002205535700002105557700002005578700002005598700002105618700002105639700002205660700001805682700002705700700002505727700002505752700002205777700002005799700002005819700002405839700002005863700002405883700002005907700002105927700001905948710007305967856003606040 2012 eng d a1546-171800aLarge-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.0 aLargescale association analyses identify new loci influencing gl c2012 Sep a991-10050 v443 aThrough genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
10aAdult10aAnimals10aBlood Glucose10aFasting10aFemale10aGene Frequency10aGenome-Wide Association Study10aHumans10aInsulin10aMale10aMetabolic Networks and Pathways10aMice10aOsmolar Concentration10aQuantitative Trait Loci1 aScott, Robert, A1 aLagou, Vasiliki1 aWelch, Ryan, P1 aWheeler, Eleanor1 aMontasser, May, E1 aLuan, Jian'an1 aMägi, Reedik1 aStrawbridge, Rona, J1 aRehnberg, Emil1 aGustafsson, Stefan1 aKanoni, Stavroula1 aRasmussen-Torvik, Laura, J1 aYengo, Loic1 aLecoeur, Cécile1 aShungin, Dmitry1 aSanna, Serena1 aSidore, Carlo1 aJohnson, Paul, C D1 aJukema, Wouter1 aJohnson, Toby1 aMahajan, Anubha1 aVerweij, Niek1 aThorleifsson, Gudmar1 aHottenga, Jouke-Jan1 aShah, Sonia1 aSmith, Albert, V1 aSennblad, Bengt1 aGieger, Christian1 aSalo, Perttu1 aPerola, Markus1 aTimpson, Nicholas, J1 aEvans, David, M1 aSt Pourcain, Beate1 aWu, Ying1 aAndrews, Jeanette, S1 aHui, Jennie1 aBielak, Lawrence, F1 aZhao, Wei1 aHorikoshi, Momoko1 aNavarro, Pau1 aIsaacs, Aaron1 aO'Connell, Jeffrey, R1 aStirrups, Kathleen1 aVitart, Veronique1 aHayward, Caroline1 aEsko, Tõnu1 aMihailov, Evelin1 aFraser, Ross, M1 aFall, Tove1 aVoight, Benjamin, F1 aRaychaudhuri, Soumya1 aChen, Han1 aLindgren, Cecilia, M1 aMorris, Andrew, P1 aRayner, Nigel, W1 aRobertson, Neil1 aRybin, Denis1 aLiu, Ching-Ti1 aBeckmann, Jacques, S1 aWillems, Sara, M1 aChines, Peter, S1 aJackson, Anne, U1 aKang, Hyun, Min1 aStringham, Heather, M1 aSong, Kijoung1 aTanaka, Toshiko1 aPeden, John, F1 aGoel, Anuj1 aHicks, Andrew, A1 aAn, Ping1 aMüller-Nurasyid, Martina1 aFranco-Cereceda, Anders1 aFolkersen, Lasse1 aMarullo, Letizia1 aJansen, Hanneke1 aOldehinkel, Albertine, J1 aBruinenberg, Marcel1 aPankow, James, S1 aNorth, Kari, E1 aForouhi, Nita, G1 aLoos, Ruth, J F1 aEdkins, Sarah1 aVarga, Tibor, V1 aHallmans, Göran1 aOksa, Heikki1 aAntonella, Mulas1 aNagaraja, Ramaiah1 aTrompet, Stella1 aFord, Ian1 aBakker, Stephan, J L1 aKong, Augustine1 aKumari, Meena1 aGigante, Bruna1 aHerder, Christian1 aMunroe, Patricia, B1 aCaulfield, Mark1 aAntti, Jula1 aMangino, Massimo1 aSmall, Kerrin1 aMiljkovic, Iva1 aLiu, Yongmei1 aAtalay, Mustafa1 aKiess, Wieland1 aJames, Alan, L1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aPalmer, Colin, N A1 aDoney, Alex, S F1 aWillemsen, Gonneke1 aSmit, Johannes, H1 aCampbell, Susan1 aPolasek, Ozren1 aBonnycastle, Lori, L1 aHercberg, Serge1 aDimitriou, Maria1 aBolton, Jennifer, L1 aFowkes, Gerard, R1 aKovacs, Peter1 aLindström, Jaana1 aZemunik, Tatijana1 aBandinelli, Stefania1 aWild, Sarah, H1 aBasart, Hanneke, V1 aRathmann, Wolfgang1 aGrallert, Harald1 aMaerz, Winfried1 aKleber, Marcus, E1 aBoehm, Bernhard, O1 aPeters, Annette1 aPramstaller, Peter, P1 aProvince, Michael, A1 aBorecki, Ingrid, B1 aHastie, Nicholas, D1 aRudan, Igor1 aCampbell, Harry1 aWatkins, Hugh1 aFarrall, Martin1 aStumvoll, Michael1 aFerrucci, Luigi1 aWaterworth, Dawn, M1 aBergman, Richard, N1 aCollins, Francis, S1 aTuomilehto, Jaakko1 aWatanabe, Richard, M1 aGeus, Eco, J C1 aPenninx, Brenda, W1 aHofman, Albert1 aOostra, Ben, A1 aPsaty, Bruce, M1 aVollenweider, Peter1 aWilson, James, F1 aWright, Alan, F1 aHovingh, Kees1 aMetspalu, Andres1 aUusitupa, Matti1 aMagnusson, Patrik, K E1 aKyvik, Kirsten, O1 aKaprio, Jaakko1 aPrice, Jackie, F1 aDedoussis, George, V1 aDeloukas, Panos1 aMeneton, Pierre1 aLind, Lars1 aBoehnke, Michael1 aShuldiner, Alan, R1 aDuijn, Cornelia, M1 aMorris, Andrew, D1 aToenjes, Anke1 aPeyser, Patricia, A1 aBeilby, John, P1 aKörner, Antje1 aKuusisto, Johanna1 aLaakso, Markku1 aBornstein, Stefan, R1 aSchwarz, Peter, E H1 aLakka, Timo, A1 aRauramaa, Rainer1 aAdair, Linda, S1 aSmith, George Davey1 aSpector, Tim, D1 aIllig, Thomas1 ade Faire, Ulf1 aHamsten, Anders1 aGudnason, Vilmundur1 aKivimaki, Mika1 aHingorani, Aroon1 aKeinanen-Kiukaanniemi, Sirkka, M1 aSaaristo, Timo, E1 aBoomsma, Dorret, I1 aStefansson, Kari1 aHarst, Pim1 aDupuis, Josée1 aPedersen, Nancy, L1 aSattar, Naveed1 aHarris, Tamara, B1 aCucca, Francesco1 aRipatti, Samuli1 aSalomaa, Veikko1 aMohlke, Karen, L1 aBalkau, Beverley1 aFroguel, Philippe1 aPouta, Anneli1 aJarvelin, Marjo-Riitta1 aWareham, Nicholas, J1 aBouatia-Naji, Nabila1 aMcCarthy, Mark, I1 aFranks, Paul, W1 aMeigs, James, B1 aTeslovich, Tanya, M1 aFlorez, Jose, C1 aLangenberg, Claudia1 aIngelsson, Erik1 aProkopenko, Inga1 aBarroso, Inês1 aDIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium uhttps://chs-nhlbi.org/node/609121848nas a2207177 4500008004100000022001400041245015100055210006900206260000900275300001300284490000600297520178200303653001602085653002202101653003702123653002102160653003002181653004002211653001102251653002002262653003802282653003402320653002702354653001102381653002302392653000902415653003602424653003602460653002002496100001802516700002502534700002202559700002102581700001402602700002102616700002002637700001802657700002002675700002802695700002702723700002002750700002202770700001802792700001802810700002002828700002002848700001702868700001102885700002202896700002102918700001602939700001302955700002402968700003102992700002603023700002203049700001903071700002203090700001803112700001903130700002303149700002403172700002003196700001903216700002503235700002403260700001703284700002403301700001903325700002103344700002003365700002303385700002003408700002203428700002003450700001403470700001903484700002003503700002603523700002003549700002303569700001903592700002003611700002503631700002103656700002303677700002303700700002203723700002203745700002303767700002403790700002103814700001903835700002003854700001703874700001703891700001803908700002203926700002003948700001903968700002103987700002104008700002604029700002004055700002104075700002104096700002004117700001704137700001804154700001904172700002404191700002404215700001904239700002204258700002104280700002304301700002804324700002504352700001704377700001704394700002404411700002404435700002004459700002004479700001604499700001904515700002004534700002004554700002004574700002304594700002504617700002104642700002204663700002404685700002404709700002404733700002004757700002004777700002404797700002004821700001904841700002004860700002404880700002004904700003204924700002004956700001904976700002404995700001905019700002405038700002505062700002405087700002105111700002105132700001605153700001705169700002305186700002505209700002405234700002305258700002305281700001605304700001705320700002005337700002105357700002305378700002305401700001905424700002105443700002505464700003405489700002105523700002405544700001905568700002705587700002105614700002205635700001905657700002105676700002605697700002305723700002205746700002105768700002905789700001905818700002205837700001805859700001605877700001905893700002705912700002205939700001805961700002205979700002206001700001506023700002106038700002306059700002306082700001806105700002006123700001706143700002206160700002306182700001206205700002306217700002506240700002306265700001806288700002206306700002406328700002106352700001906373700001906392700002306411700002006434700002606454700001706480700002406497700002106521700002306542700002006565700002306585700002406608700001906632700002406651700001806675700002506693700001906718700002306737700002006760700002406780700002606804700001206830700001806842700002106860700001706881700002206898700002006920700002606940700002106966700003506987700002207022700002307044700002007067700002507087700002407112700002107136700002407157700001907181700002007200700001907220700002107239700002207260700001907282700002107301700002007322700001907342700002207361700002307383700001607406700002007422700002207442700002307464700002407487700001707511700002507528700002507553700002307578700002007601700001807621700002607639700001907665700001907684700001607703700001607719700002807735700002107763700001807784700002207802700002307824700002107847700002107868700002107889700002207910700002007932700002107952700002207973700002507995700001808020700002008038700001808058700001708076700001908093700002408112700001808136700001508154700001908169700001608188700003508204700001808239700002508257700001908282700002008301700001308321700002308334700001808357700002008375700002508395700002708420700002208447700002408469700002008493700001908513700002008532700002108552700001908573700002108592700002308613700002408636700002208660700001808682700002708700700002208727700001808749700001908767700002308786700002308809700002008832700001808852700001908870700002308889700002308912700002808935700002108963700002708984700001709011700002209028700002309050700001809073700002009091700002109111700001909132700001609151700002809167700002209195700002009217700002009237700002209257700002409279700001609303700001409319700002109333700001909354700002509373700001909398700002109417700002009438700001809458700002309476700002109499700002209520700002409542700002109566700001209587700001909599700002109618700003609639700002309675700002009698700002309718700001809741700001709759700002509776700002209801700001909823700002409842700001709866700001609883700002309899700002209922700002009944700001909964700002309983700002710006700001910033700001910052700002310071700002110094700001810115700002510133700002110158700001810179700002010197700002610217700002110243700002210264700002210286700001810308700002210326700001710348700001710365700002210382700002210404700002410426700002510450700002110475700001910496700002210515700002310537700001610560700001510576700001910591700002810610700001810638700002810656700002110684700001810705700002710723700002210750700002310772700002010795700002110815700001910836700001710855700001810872700001910890700002310909700002910932700002310961700002010984700002211004700001811026700001911044700002511063700002311088700002011111700002711131700002111158700002411179700002011203700002511223700001911248700002211267700001911289700002311308700001811331700002611349700001511375700002011390700001711410700002011427700001811447700002011465700002011485700002811505700002011533700002211553700002011575700002411595700001911619700002211638700002711660700002311687700001711710700002011727700002411747700001711771700001911788700002711807700002011834700002011854700001911874700002011893700002111913700002511934700002611959700002111985700002612006700002312032700002912055700002412084700002012108700001912128700002312147700001912170700002112189700002512210700001912235700001612254700001612270700001912286700001612305700002012321700002012341700001812361700001612379700001712395700002312412700003012435700002112465700002112486700002112507700001812528700002112546700002312567700002212590700001712612700002012629700002212649700001912671700001712690700002012707700002012727700001912747700002012766700001712786700002012803700002112823700003012844700002412874700002612898700002512924700001912949700001812968700002412986700001913010700001713029700001813046700002313064700002213087700002213109700002313131700002113154700002213175700002013197700001813217700001913235700001913254700002613273700001613299700001813315700002813333700002213361700002413383700002213407700002313429700002213452700001913474700002013493700002313513700002213536700002213558700002013580700002413600700002313624700002513647700001813672700002213690700002113712700002313733700002413756700002913780700002413809700002013833700001813853700001813871700002113889700002713910700002213937700002313959700001613982700002413998700002214022700002114044700002414065700002214089700001814111700002214129700002514151700002014176700002314196700002414219700002214243700002414265700002514289700002514314700002014339700002114359700002214380710002414402710002114426710002314447710002214470710002314492710002114515710002914536710002514565710002414590710002014614856003614634 2012 eng d a1553-740400aNovel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.0 aNovel loci for adiponectin levels and their influence on type 2 c2012 ae10026070 v83 aCirculating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
10aAdiponectin10aAfrican Americans10aAsian Continental Ancestry Group10aCholesterol, HDL10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aFemale10aGene Expression10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGlucose Tolerance Test10aHumans10aInsulin Resistance10aMale10aMetabolic Networks and Pathways10aPolymorphism, Single Nucleotide10aWaist-Hip Ratio1 aDastani, Zari1 aHivert, Marie-France1 aTimpson, Nicholas1 aPerry, John, R B1 aYuan, Xin1 aScott, Robert, A1 aHenneman, Peter1 aHeid, Iris, M1 aKizer, Jorge, R1 aLyytikäinen, Leo-Pekka1 aFuchsberger, Christian1 aTanaka, Toshiko1 aMorris, Andrew, P1 aSmall, Kerrin1 aIsaacs, Aaron1 aBeekman, Marian1 aCoassin, Stefan1 aLohman, Kurt1 aQi, Lu1 aKanoni, Stavroula1 aPankow, James, S1 aUh, Hae-Won1 aWu, Ying1 aBidulescu, Aurelian1 aRasmussen-Torvik, Laura, J1 aGreenwood, Celia, M T1 aLadouceur, Martin1 aGrimsby, Jonna1 aManning, Alisa, K1 aLiu, Ching-Ti1 aKooner, Jaspal1 aMooser, Vincent, E1 aVollenweider, Peter1 aKapur, Karen, A1 aChambers, John1 aWareham, Nicholas, J1 aLangenberg, Claudia1 aFrants, Rune1 aWillems-Vandijk, Ko1 aOostra, Ben, A1 aWillems, Sara, M1 aLamina, Claudia1 aWinkler, Thomas, W1 aPsaty, Bruce, M1 aTracy, Russell, P1 aBrody, Jennifer1 aChen, Ida1 aViikari, Jorma1 aKähönen, Mika1 aPramstaller, Peter, P1 aEvans, David, M1 aSt Pourcain, Beate1 aSattar, Naveed1 aWood, Andrew, R1 aBandinelli, Stefania1 aCarlson, Olga, D1 aEgan, Josephine, M1 aBöhringer, Stefan1 avan Heemst, Diana1 aKedenko, Lyudmyla1 aKristiansson, Kati1 aNuotio, Marja-Liisa1 aLoo, Britt-Marie1 aHarris, Tamara1 aGarcia, Melissa1 aKanaya, Alka1 aHaun, Margot1 aKlopp, Norman1 aWichmann, H-Erich1 aDeloukas, Panos1 aKatsareli, Efi1 aCouper, David, J1 aDuncan, Bruce, B1 aKloppenburg, Margreet1 aAdair, Linda, S1 aBorja, Judith, B1 aWilson, James, G1 aMusani, Solomon1 aGuo, Xiuqing1 aJohnson, Toby1 aSemple, Robert1 aTeslovich, Tanya, M1 aAllison, Matthew, A1 aRedline, Susan1 aBuxbaum, Sarah, G1 aMohlke, Karen, L1 aMeulenbelt, Ingrid1 aBallantyne, Christie, M1 aDedoussis, George, V1 aHu, Frank, B1 aLiu, Yongmei1 aPaulweber, Bernhard1 aSpector, Timothy, D1 aSlagboom, Eline1 aFerrucci, Luigi1 aJula, Antti1 aPerola, Markus1 aRaitakari, Olli1 aFlorez, Jose, C1 aSalomaa, Veikko1 aEriksson, Johan, G1 aFrayling, Timothy, M1 aHicks, Andrew, A1 aLehtimäki, Terho1 aSmith, George Davey1 aSiscovick, David, S1 aKronenberg, Florian1 aDuijn, Cornelia1 aLoos, Ruth, J F1 aWaterworth, Dawn, M1 aMeigs, James, B1 aDupuis, Josée1 aRichards, Brent1 aVoight, Benjamin, F1 aScott, Laura, J1 aSteinthorsdottir, Valgerdur1 aDina, Christian1 aWelch, Ryan, P1 aZeggini, Eleftheria1 aHuth, Cornelia1 aAulchenko, Yurii, S1 aThorleifsson, Gudmar1 aMcCulloch, Laura, J1 aFerreira, Teresa1 aGrallert, Harald1 aAmin, Najaf1 aWu, Guanming1 aWiller, Cristen, J1 aRaychaudhuri, Soumya1 aMcCarroll, Steve, A1 aHofmann, Oliver, M1 aSegrè, Ayellet, V1 aHoek, Mandy1 aNavarro, Pau1 aArdlie, Kristin1 aBalkau, Beverley1 aBenediktsson, Rafn1 aBennett, Amanda, J1 aBlagieva, Roza1 aBoerwinkle, Eric1 aBonnycastle, Lori, L1 aBoström, Kristina, Bengtsson1 aBravenboer, Bert1 aBumpstead, Suzannah1 aBurtt, Noel, P1 aCharpentier, Guillaume1 aChines, Peter, S1 aCornelis, Marilyn1 aCrawford, Gabe1 aDoney, Alex, S F1 aElliott, Katherine, S1 aElliott, Amanda, L1 aErdos, Michael, R1 aFox, Caroline, S1 aFranklin, Christopher, S1 aGanser, Martha1 aGieger, Christian1 aGrarup, Niels1 aGreen, Todd1 aGriffin, Simon1 aGroves, Christopher, J1 aGuiducci, Candace1 aHadjadj, Samy1 aHassanali, Neelam1 aHerder, Christian1 aIsomaa, Bo1 aJackson, Anne, U1 aJohnson, Paul, R V1 aJørgensen, Torben1 aKao, Wen, H L1 aKong, Augustine1 aKraft, Peter1 aKuusisto, Johanna1 aLauritzen, Torsten1 aLi, Man1 aLieverse, Aloysius1 aLindgren, Cecilia, M1 aLyssenko, Valeriya1 aMarre, Michel1 aMeitinger, Thomas1 aMidthjell, Kristian1 aMorken, Mario, A1 aNarisu, Narisu1 aNilsson, Peter1 aOwen, Katharine, R1 aPayne, Felicity1 aPetersen, Ann-Kristin1 aPlatou, Carl1 aProença, Christine1 aProkopenko, Inga1 aRathmann, Wolfgang1 aRayner, William1 aRobertson, Neil, R1 aRocheleau, Ghislain1 aRoden, Michael1 aSampson, Michael, J1 aSaxena, Richa1 aShields, Beverley, M1 aShrader, Peter1 aSigurdsson, Gunnar1 aSparsø, Thomas1 aStrassburger, Klaus1 aStringham, Heather, M1 aSun, Qi1 aSwift, Amy, J1 aThorand, Barbara1 aTichet, Jean1 aTuomi, Tiinamaija1 avan Dam, Rob, M1 avan Haeften, Timon, W1 avan Herpt, Thijs1 avan Vliet-Ostaptchouk, Jana, V1 aWalters, Bragi, G1 aWeedon, Michael, N1 aWijmenga, Cisca1 aWitteman, Jacqueline1 aBergman, Richard, N1 aCauchi, Stephane1 aCollins, Francis, S1 aGloyn, Anna, L1 aGyllensten, Ulf1 aHansen, Torben1 aHide, Winston, A1 aHitman, Graham, A1 aHofman, Albert1 aHunter, David, J1 aHveem, Kristian1 aLaakso, Markku1 aMorris, Andrew, D1 aPalmer, Colin, N A1 aRudan, Igor1 aSijbrands, Eric1 aStein, Lincoln, D1 aTuomilehto, Jaakko1 aUitterlinden, Andre1 aWalker, Mark1 aWatanabe, Richard, M1 aAbecasis, Goncalo, R1 aBoehm, Bernhard, O1 aCampbell, Harry1 aDaly, Mark, J1 aHattersley, Andrew, T1 aPedersen, Oluf1 aBarroso, Inês1 aGroop, Leif1 aSladek, Rob1 aThorsteinsdottir, Unnur1 aWilson, James, F1 aIllig, Thomas1 aFroguel, Philippe1 aDuijn, Cornelia, M1 aStefansson, Kari1 aAltshuler, David1 aBoehnke, Michael1 aMcCarthy, Mark, I1 aSoranzo, Nicole1 aWheeler, Eleanor1 aGlazer, Nicole, L1 aBouatia-Naji, Nabila1 aMägi, Reedik1 aRandall, Joshua1 aElliott, Paul1 aRybin, Denis1 aDehghan, Abbas1 aHottenga, Jouke Jan1 aSong, Kijoung1 aGoel, Anuj1 aLajunen, Taina1 aDoney, Alex1 aCavalcanti-Proença, Christine1 aKumari, Meena1 aTimpson, Nicholas, J1 aZabena, Carina1 aIngelsson, Erik1 aAn, Ping1 aO'Connell, Jeffrey1 aLuan, Jian'an1 aElliott, Amanda1 aMcCarroll, Steven, A1 aRoccasecca, Rosa Maria1 aPattou, François1 aSethupathy, Praveen1 aAriyurek, Yavuz1 aBarter, Philip1 aBeilby, John, P1 aBen-Shlomo, Yoav1 aBergmann, Sven1 aBochud, Murielle1 aBonnefond, Amélie1 aBorch-Johnsen, Knut1 aBöttcher, Yvonne1 aBrunner, Eric1 aBumpstead, Suzannah, J1 aChen, Yii-Der Ida1 aChines, Peter1 aClarke, Robert1 aCoin, Lachlan, J M1 aCooper, Matthew, N1 aCrisponi, Laura1 aDay, Ian, N M1 aGeus, Eco, J C1 aDelplanque, Jerome1 aFedson, Annette, C1 aFischer-Rosinsky, Antje1 aForouhi, Nita, G1 aFranzosi, Maria Grazia1 aGalan, Pilar1 aGoodarzi, Mark, O1 aGraessler, Jürgen1 aGrundy, Scott1 aGwilliam, Rhian1 aHallmans, Göran1 aHammond, Naomi1 aHan, Xijing1 aHartikainen, Anna-Liisa1 aHayward, Caroline1 aHeath, Simon, C1 aHercberg, Serge1 aHillman, David, R1 aHingorani, Aroon, D1 aHui, Jennie1 aHung, Joe1 aKaakinen, Marika1 aKaprio, Jaakko1 aKesaniemi, Antero, Y1 aKivimaki, Mika1 aKnight, Beatrice1 aKoskinen, Seppo1 aKovacs, Peter1 aKyvik, Kirsten Ohm1 aLathrop, Mark, G1 aLawlor, Debbie, A1 aLe Bacquer, Olivier1 aLecoeur, Cécile1 aLi, Yun1 aMahley, Robert1 aMangino, Massimo1 aMartínez-Larrad, María Teresa1 aMcAteer, Jarred, B1 aMcPherson, Ruth1 aMeisinger, Christa1 aMelzer, David1 aMeyre, David1 aMitchell, Braxton, D1 aMukherjee, Sutapa1 aNaitza, Silvia1 aNeville, Matthew, J1 aOrrù, Marco1 aPakyz, Ruth1 aPaolisso, Giuseppe1 aPattaro, Cristian1 aPearson, Daniel1 aPeden, John, F1 aPedersen, Nancy, L1 aPfeiffer, Andreas, F H1 aPichler, Irene1 aPolasek, Ozren1 aPosthuma, Danielle1 aPotter, Simon, C1 aPouta, Anneli1 aProvince, Michael, A1 aRayner, Nigel, W1 aRice, Kenneth1 aRipatti, Samuli1 aRivadeneira, Fernando1 aRolandsson, Olov1 aSandbaek, Annelli1 aSandhu, Manjinder1 aSanna, Serena1 aSayer, Avan Aihie1 aScheet, Paul1 aSeedorf, Udo1 aSharp, Stephen, J1 aShields, Beverley1 aSigurðsson, Gunnar1 aSijbrands, Eric, J G1 aSilveira, Angela1 aSimpson, Laila1 aSingleton, Andrew1 aSmith, Nicholas, L1 aSovio, Ulla1 aSwift, Amy1 aSyddall, Holly1 aSyvänen, Ann-Christine1 aTönjes, Anke1 aUitterlinden, André, G1 aDijk, Ko Willems1 aVarma, Dhiraj1 aVisvikis-Siest, Sophie1 aVitart, Veronique1 aVogelzangs, Nicole1 aWaeber, Gérard1 aWagner, Peter, J1 aWalley, Andrew1 aWard, Kim, L1 aWatkins, Hugh1 aWild, Sarah, H1 aWillemsen, Gonneke1 aWitteman, Jaqueline, C M1 aYarnell, John, W G1 aZelenika, Diana1 aZethelius, Björn1 aZhai, Guangju1 aZhao, Jing Hua1 aZillikens, Carola, M1 aBorecki, Ingrid, B1 aMeneton, Pierre1 aMagnusson, Patrik, K E1 aNathan, David, M1 aWilliams, Gordon, H1 aSilander, Kaisa1 aBornstein, Stefan, R1 aSchwarz, Peter1 aSpranger, Joachim1 aKarpe, Fredrik1 aShuldiner, Alan, R1 aCooper, Cyrus1 aSerrano-Ríos, Manuel1 aLind, Lars1 aPalmer, Lyle, J1 aHu, Frank, B1 aFranks, Paul, W1 aEbrahim, Shah1 aMarmot, Michael1 aKao, Linda, W H1 aPramstaller, Peter Paul1 aWright, Alan, F1 aStumvoll, Michael1 aHamsten, Anders1 aBuchanan, Thomas, A1 aValle, Timo, T1 aRotter, Jerome, I1 aPenninx, Brenda, W J H1 aBoomsma, Dorret, I1 aCao, Antonio1 aScuteri, Angelo1 aSchlessinger, David1 aUda, Manuela1 aRuokonen, Aimo1 aJarvelin, Marjo-Riitta1 aPeltonen, Leena1 aMooser, Vincent1 aSladek, Robert1 aMusunuru, Kiran1 aSmith, Albert, V1 aEdmondson, Andrew, C1 aStylianou, Ioannis, M1 aKoseki, Masahiro1 aPirruccello, James, P1 aChasman, Daniel, I1 aJohansen, Christopher, T1 aFouchier, Sigrid, W1 aPeloso, Gina, M1 aBarbalic, Maja1 aRicketts, Sally, L1 aBis, Joshua, C1 aFeitosa, Mary, F1 aOrho-Melander, Marju1 aMelander, Olle1 aLi, Xiaohui1 aLi, Mingyao1 aCho, Yoon Shin1 aGo, Min Jin1 aKim, Young, Jin1 aLee, Jong-Young1 aPark, Taesung1 aKim, Kyunga1 aSim, Xueling1 aOng, Rick Twee-Hee1 aCroteau-Chonka, Damien, C1 aLange, Leslie, A1 aSmith, Joshua, D1 aZiegler, Andreas1 aZhang, Weihua1 aZee, Robert, Y L1 aWhitfield, John, B1 aThompson, John, R1 aSurakka, Ida1 aSpector, Tim, D1 aSmit, Johannes, H1 aSinisalo, Juha1 aScott, James1 aSaharinen, Juha1 aSabatti, Chiara1 aRose, Lynda, M1 aRoberts, Robert1 aRieder, Mark1 aParker, Alex, N1 aParé, Guillaume1 aO'Donnell, Christopher, J1 aNieminen, Markku, S1 aNickerson, Deborah, A1 aMontgomery, Grant, W1 aMcArdle, Wendy1 aMasson, David1 aMartin, Nicholas, G1 aMarroni, Fabio1 aLucas, Gavin1 aLuben, Robert1 aLokki, Marja-Liisa1 aLettre, Guillaume1 aLauner, Lenore, J1 aLakatta, Edward, G1 aLaaksonen, Reijo1 aKyvik, Kirsten, O1 aKönig, Inke, R1 aKhaw, Kay-Tee1 aKaplan, Lee, M1 aJohansson, Asa1 aJanssens, Cecile, J W1 aIgl, Wilmar1 aHovingh, Kees1 aHengstenberg, Christian1 aHavulinna, Aki, S1 aHastie, Nicholas, D1 aHarris, Tamara, B1 aHaritunians, Talin1 aHall, Alistair, S1 aGroop, Leif, C1 aGonzalez, Elena1 aFreimer, Nelson, B1 aErdmann, Jeanette1 aEjebe, Kenechi, G1 aDöring, Angela1 aDominiczak, Anna, F1 aDemissie, Serkalem1 aDeloukas, Panagiotis1 ade Faire, Ulf1 aCrawford, Gabriel1 aChen, Yii-der, I1 aCaulfield, Mark, J1 aBoekholdt, Matthijs1 aAssimes, Themistocles, L1 aQuertermous, Thomas1 aSeielstad, Mark1 aWong, Tien, Y1 aTai, E-Shyong1 aFeranil, Alan, B1 aKuzawa, Christopher, W1 aTaylor, Herman, A1 aGabriel, Stacey, B1 aHolm, Hilma1 aGudnason, Vilmundur1 aKrauss, Ronald, M1 aOrdovas, Jose, M1 aMunroe, Patricia, B1 aKooner, Jaspal, S1 aTall, Alan, R1 aHegele, Robert, A1 aKastelein, John, J P1 aSchadt, Eric, E1 aStrachan, David, P1 aReilly, Muredach, P1 aSamani, Nilesh, J1 aSchunkert, Heribert1 aCupples, Adrienne, L1 aSandhu, Manjinder, S1 aRidker, Paul, M1 aRader, Daniel, J1 aKathiresan, Sekar1 aDIAGRAM+ Consortium1 aMAGIC Consortium1 aGLGC Investigators1 aMuTHER Consortium1 aDIAGRAM Consortium1 aGIANT Consortium1 aGlobal B Pgen Consortium1 aProcardis Consortium1 aMAGIC investigators1 aGLGC Consortium uhttps://chs-nhlbi.org/node/137810059nas a2203157 4500008004100000022001400041245012200055210006900177260001300246300001100259490000700270520116100277653001001438653000901448653002501457653002201482653002701504653002401531653001101555653003801566653003401604653001301638653002101651653001101672653002101683653000901704653001601713653001501729653003601744100001901780700001901799700001601818700001501834700002401849700002401873700002201897700002501919700002001944700001801964700002301982700001902005700002802024700002502052700002202077700001902099700002302118700001802141700003002159700002502189700001902214700002602233700001902259700001802278700002502296700002102321700001902342700001902361700002802380700002102408700001802429700002202447700002202469700001702491700001802508700002002526700002102546700002302567700002302590700001802613700002302631700002002654700002502674700002302699700002302722700002602745700001802771700002202789700002502811700002302836700002502859700002102884700002202905700002202927700002302949700001902972700001902991700001703010700002003027700002003047700002103067700002503088700001803113700002303131700002203154700002403176700002003200700001803220700002203238700003903260700001703299700002103316700002203337700002303359700002003382700002203402700001803424700001903442700002003461700001903481700001803500700002003518700001603538700002803554700002103582700001803603700002303621700002003644700002103664700002203685700003003707700001703737700001703754700002203771700002103793700002403814700002103838700002403859700002203883700001603905700002203921700002203943700002103965700001903986700001904005700001904024700001804043700002404061700001904085700002304104700002204127700002004149700001904169700002204188700002204210700002004232700002004252700001804272700002204290700002604312700002304338700001704361700003104378700002704409700001804436700002404454700001804478700002304496700002004519700002704539700002404566700003004590700001704620700002004637700002004657700001904677700002104696700002404717700002404741700002504765700002304790700002604813700002604839700002704865700002604892700001604918700002204934700002004956700001904976700002504995700001805020700002705038700002405065700001805089700002905107700002805136700002005164700002205184700002105206700001905227700001705246700002805263700003005291700002205321700002005343700001905363700002505382700002305407700002105430700001705451700002405468700001705492700002605509700001705535700002005552700002405572700001905596700001505615700002205630700002805652700001905680700002005699700001805719700002305737700002205760700001905782700001905801700001705820700002605837700002405863700002305887700002405910700002005934700002205954700002405976700002506000700002306025700002006048700002006068700002106088700002106109700001606130700001806146700002606164700002606190700002506216700002406241700001806265700001706283700002306300700002406323700002406347700002006371700002006391700002206411700001806433700002406451700002306475700002106498700002106519700002306540700002106563700001706584700002306601700001906624700002606643700002506669700001806694700002506712700002906737710002006766710002206786710001406808710002206822710002106844856003606865 2014 eng d a1546-171800aGenetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.0 aGenetic association study of QT interval highlights role for cal c2014 Aug a826-360 v463 aThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
10aAdult10aAged10aArrhythmias, Cardiac10aCalcium Signaling10aDeath, Sudden, Cardiac10aElectrocardiography10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHeart Ventricles10aHumans10aLong QT Syndrome10aMale10aMiddle Aged10aMyocardium10aPolymorphism, Single Nucleotide1 aArking, Dan, E1 aPulit, Sara, L1 aCrotti, Lia1 aHarst, Pim1 aMunroe, Patricia, B1 aKoopmann, Tamara, T1 aSotoodehnia, Nona1 aRossin, Elizabeth, J1 aMorley, Michael1 aWang, Xinchen1 aJohnson, Andrew, D1 aLundby, Alicia1 aGudbjartsson, Daniel, F1 aNoseworthy, Peter, A1 aEijgelsheim, Mark1 aBradford, Yuki1 aTarasov, Kirill, V1 aDörr, Marcus1 aMüller-Nurasyid, Martina1 aLahtinen, Annukka, M1 aNolte, Ilja, M1 aSmith, Albert, Vernon1 aBis, Joshua, C1 aIsaacs, Aaron1 aNewhouse, Stephen, J1 aEvans, Daniel, S1 aPost, Wendy, S1 aWaggott, Daryl1 aLyytikäinen, Leo-Pekka1 aHicks, Andrew, A1 aEisele, Lewin1 aEllinghaus, David1 aHayward, Caroline1 aNavarro, Pau1 aUlivi, Sheila1 aTanaka, Toshiko1 aTester, David, J1 aChatel, Stéphanie1 aGustafsson, Stefan1 aKumari, Meena1 aMorris, Richard, W1 aNaluai, Åsa, T1 aPadmanabhan, Sandosh1 aKluttig, Alexander1 aStrohmer, Bernhard1 aPanayiotou, Andrie, G1 aTorres, Maria1 aKnoflach, Michael1 aHubacek, Jaroslav, A1 aSlowikowski, Kamil1 aRaychaudhuri, Soumya1 aKumar, Runjun, D1 aHarris, Tamara, B1 aLauner, Lenore, J1 aShuldiner, Alan, R1 aAlonso, Alvaro1 aBader, Joel, S1 aEhret, Georg1 aHuang, Hailiang1 aKao, Linda, W H1 aStrait, James, B1 aMacfarlane, Peter, W1 aBrown, Morris1 aCaulfield, Mark, J1 aSamani, Nilesh, J1 aKronenberg, Florian1 aWilleit, Johann1 aSmith, Gustav1 aGreiser, Karin, H1 aSchwabedissen, Henriette, Meyer Zu1 aWerdan, Karl1 aCarella, Massimo1 aZelante, Leopoldo1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aRotter, Jerome, I1 aKolcic, Ivana1 aPolasek, Ozren1 aWright, Alan, F1 aGriffin, Maura1 aDaly, Mark, J1 aArnar, David, O1 aHolm, Hilma1 aThorsteinsdottir, Unnur1 aDenny, Joshua, C1 aRoden, Dan, M1 aZuvich, Rebecca, L1 aEmilsson, Valur1 aPlump, Andrew, S1 aLarson, Martin, G1 aO'Donnell, Christopher, J1 aYin, Xiaoyan1 aBobbo, Marco1 aD'Adamo, Adamo, P1 aIorio, Annamaria1 aSinagra, Gianfranco1 aCarracedo, Angel1 aCummings, Steven, R1 aNalls, Michael, A1 aJula, Antti1 aKontula, Kimmo, K1 aMarjamaa, Annukka1 aOikarinen, Lasse1 aPerola, Markus1 aPorthan, Kimmo1 aErbel, Raimund1 aHoffmann, Per1 aJöckel, Karl-Heinz1 aKälsch, Hagen1 aNöthen, Markus, M1 aHoed, Marcel, den1 aLoos, Ruth, J F1 aThelle, Dag, S1 aGieger, Christian1 aMeitinger, Thomas1 aPerz, Siegfried1 aPeters, Annette1 aPrucha, Hanna1 aSinner, Moritz, F1 aWaldenberger, Melanie1 ade Boer, Rudolf, A1 aFranke, Lude1 avan der Vleuten, Pieter, A1 aBeckmann, Britt, Maria1 aMartens, Eimo1 aBardai, Abdennasser1 aHofman, Nynke1 aWilde, Arthur, A M1 aBehr, Elijah, R1 aDalageorgou, Chrysoula1 aGiudicessi, John, R1 aMedeiros-Domingo, Argelia1 aBarc, Julien1 aKyndt, Florence1 aProbst, Vincent1 aGhidoni, Alice1 aInsolia, Roberto1 aHamilton, Robert, M1 aScherer, Stephen, W1 aBrandimarto, Jeffrey1 aMargulies, Kenneth1 aMoravec, Christine, E1 aM, Fabiola, del Greco1 aFuchsberger, Christian1 aO'Connell, Jeffrey, R1 aLee, Wai, K1 aWatt, Graham, C M1 aCampbell, Harry1 aWild, Sarah, H1 aMokhtari, Nour, E El1 aFrey, Norbert1 aAsselbergs, Folkert, W1 aLeach, Irene, Mateo1 aNavis, Gerjan1 avan den Berg, Maarten, P1 avan Veldhuisen, Dirk, J1 aKellis, Manolis1 aKrijthe, Bouwe, P1 aFranco, Oscar, H1 aHofman, Albert1 aKors, Jan, A1 aUitterlinden, André, G1 aWitteman, Jacqueline, C M1 aKedenko, Lyudmyla1 aLamina, Claudia1 aOostra, Ben, A1 aAbecasis, Goncalo, R1 aLakatta, Edward, G1 aMulas, Antonella1 aOrrù, Marco1 aSchlessinger, David1 aUda, Manuela1 aMarkus, Marcello, R P1 aVölker, Uwe1 aSnieder, Harold1 aSpector, Timothy, D1 aArnlöv, Johan1 aLind, Lars1 aSundström, Johan1 aSyvänen, Ann-Christine1 aKivimaki, Mika1 aKähönen, Mika1 aMononen, Nina1 aRaitakari, Olli, T1 aViikari, Jorma, S1 aAdamkova, Vera1 aKiechl, Stefan1 aBrion, Maria1 aNicolaides, Andrew, N1 aPaulweber, Bernhard1 aHaerting, Johannes1 aDominiczak, Anna, F1 aNyberg, Fredrik1 aWhincup, Peter, H1 aHingorani, Aroon, D1 aSchott, Jean-Jacques1 aBezzina, Connie, R1 aIngelsson, Erik1 aFerrucci, Luigi1 aGasparini, Paolo1 aWilson, James, F1 aRudan, Igor1 aFranke, Andre1 aMühleisen, Thomas, W1 aPramstaller, Peter, P1 aLehtimäki, Terho, J1 aPaterson, Andrew, D1 aParsa, Afshin1 aLiu, Yongmei1 aDuijn, Cornelia, M1 aSiscovick, David, S1 aGudnason, Vilmundur1 aJamshidi, Yalda1 aSalomaa, Veikko1 aFelix, Stephan, B1 aSanna, Serena1 aRitchie, Marylyn, D1 aStricker, Bruno, H1 aStefansson, Kari1 aBoyer, Laurie, A1 aCappola, Thomas, P1 aOlsen, Jesper, V1 aLage, Kasper1 aSchwartz, Peter, J1 aKääb, Stefan1 aChakravarti, Aravinda1 aAckerman, Michael, J1 aPfeufer, Arne1 ade Bakker, Paul, I W1 aNewton-Cheh, Christopher1 aCARe Consortium1 aCOGENT Consortium1 aDCCT/EDIC1 aeMERGE Consortium1 aHRGEN Consortium uhttps://chs-nhlbi.org/node/654407420nas a2202053 4500008004100000022001400041245005000055210004800105260001600153300001200169490000700181520170000188100001501888700002401903700001801927700001801945700001701963700002401980700001802004700002402022700002202046700002202068700002202090700002102112700002202133700002802155700001902183700002002202700001902222700001802241700002002259700003002279700002102309700001802330700002202348700002202370700002602392700001802418700001902436700002202455700002502477700002302502700001602525700002502541700002502566700001902591700001802610700001902628700001702647700002402664700002002688700002102708700002602729700001702755700002502772700002502797700002602822700002402848700002002872700001402892700002202906700002202928700001702950700002102967700002302988700002103011700002403032700001903056700002003075700002003095700002103115700002003136700002003156700001803176700002503194700002203219700001703241700002303258700001703281700002203298700001703320700001903337700002503356700001503381700002203396700002103418700002003439700001903459700001603478700001803494700001903512700001903531700002103550700001903571700002403590700002303614700001803637700002003655700002003675700002003695700001803715700002503733700002603758700001903784700002303803700002503826700001703851700002503868700002203893700002303915700002403938700002403962700002203986700002504008700002404033700002204057700002304079700002404102700002404126700002004150700003204170700002104202700002404223700002004247700002304267700001704290700002804307700002804335700002304363700001904386700002204405700002304427700002204450700001704472700002604489700003204515700002104547700002004568700002804588700001504616700002304631700002404654700002004678700002004698700001604718700002104734700002704755700002804782700002304810700002004833700001904853700001804872700002204890700002104912700002504933700001904958700002104977700001904998700001905017700002405036700002205060700002305082700002305105700002905128700002105157700002205178700002005200700001605220700002905236700001805265700002205283700002505305856003605330 2016 eng d a1558-359700a52 Genetic Loci Influencing Myocardial Mass.0 a52 Genetic Loci Influencing Myocardial Mass c2016 Sep 27 a1435-480 v683 aBACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.
OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.
METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.
RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.
CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
1 aHarst, Pim1 avan Setten, Jessica1 aVerweij, Niek1 aVogler, Georg1 aFranke, Lude1 aMaurano, Matthew, T1 aWang, Xinchen1 aLeach, Irene, Mateo1 aEijgelsheim, Mark1 aSotoodehnia, Nona1 aHayward, Caroline1 aSorice, Rossella1 aMeirelles, Osorio1 aLyytikäinen, Leo-Pekka1 aPolasek, Ozren1 aTanaka, Toshiko1 aArking, Dan, E1 aUlivi, Sheila1 aTrompet, Stella1 aMüller-Nurasyid, Martina1 aSmith, Albert, V1 aDörr, Marcus1 aKerr, Kathleen, F1 aMagnani, Jared, W1 aM, Fabiola, del Greco1 aZhang, Weihua1 aNolte, Ilja, M1 aSilva, Claudia, T1 aPadmanabhan, Sandosh1 aTragante, Vinicius1 aEsko, Tõnu1 aAbecasis, Goncalo, R1 aAdriaens, Michiel, E1 aAndersen, Karl1 aBarnett, Phil1 aBis, Joshua, C1 aBodmer, Rolf1 aBuckley, Brendan, M1 aCampbell, Harry1 aCannon, Megan, V1 aChakravarti, Aravinda1 aChen, Lin, Y1 aDelitala, Alessandro1 aDevereux, Richard, B1 aDoevendans, Pieter, A1 aDominiczak, Anna, F1 aFerrucci, Luigi1 aFord, Ian1 aGieger, Christian1 aHarris, Tamara, B1 aHaugen, Eric1 aHeinig, Matthias1 aHernandez, Dena, G1 aHillege, Hans, L1 aHirschhorn, Joel, N1 aHofman, Albert1 aHubner, Norbert1 aHwang, Shih-Jen1 aIorio, Annamaria1 aKähönen, Mika1 aKellis, Manolis1 aKolcic, Ivana1 aKooner, Ishminder, K1 aKooner, Jaspal, S1 aKors, Jan, A1 aLakatta, Edward, G1 aLage, Kasper1 aLauner, Lenore, J1 aLevy, Daniel1 aLundby, Alicia1 aMacfarlane, Peter, W1 aMay, Dalit1 aMeitinger, Thomas1 aMetspalu, Andres1 aNappo, Stefania1 aNaitza, Silvia1 aNeph, Shane1 aNord, Alex, S1 aNutile, Teresa1 aOkin, Peter, M1 aOlsen, Jesper, V1 aOostra, Ben, A1 aPenninger, Josef, M1 aPennacchio, Len, A1 aPers, Tune, H1 aPerz, Siegfried1 aPeters, Annette1 aPinto, Yigal, M1 aPfeufer, Arne1 aPilia, Maria, Grazia1 aPramstaller, Peter, P1 aPrins, Bram, P1 aRaitakari, Olli, T1 aRaychaudhuri, Soumya1 aRice, Ken, M1 aRossin, Elizabeth, J1 aRotter, Jerome, I1 aSchafer, Sebastian1 aSchlessinger, David1 aSchmidt, Carsten, O1 aSehmi, Jobanpreet1 aSilljé, Herman, H W1 aSinagra, Gianfranco1 aSinner, Moritz, F1 aSlowikowski, Kamil1 aSoliman, Elsayed, Z1 aSpector, Timothy, D1 aSpiering, Wilko1 aStamatoyannopoulos, John, A1 aStolk, Ronald, P1 aStrauch, Konstantin1 aTan, Sian-Tsung1 aTarasov, Kirill, V1 aTrinh, Bosco1 aUitterlinden, André, G1 avan den Boogaard, Malou1 aDuijn, Cornelia, M1 aGilst, Wiek, H1 aViikari, Jorma, S1 aVisscher, Peter, M1 aVitart, Veronique1 aVölker, Uwe1 aWaldenberger, Melanie1 aWeichenberger, Christian, X1 aWestra, Harm-Jan1 aWijmenga, Cisca1 aWolffenbuttel, Bruce, H1 aYang, Jian1 aBezzina, Connie, R1 aMunroe, Patricia, B1 aSnieder, Harold1 aWright, Alan, F1 aRudan, Igor1 aBoyer, Laurie, A1 aAsselbergs, Folkert, W1 avan Veldhuisen, Dirk, J1 aStricker, Bruno, H1 aPsaty, Bruce, M1 aCiullo, Marina1 aSanna, Serena1 aLehtimäki, Terho1 aWilson, James, F1 aBandinelli, Stefania1 aAlonso, Alvaro1 aGasparini, Paolo1 aJukema, Wouter1 aKääb, Stefan1 aGudnason, Vilmundur1 aFelix, Stephan, B1 aHeckbert, Susan, R1 ade Boer, Rudolf, A1 aNewton-Cheh, Christopher1 aHicks, Andrew, A1 aChambers, John, C1 aJamshidi, Yalda1 aVisel, Axel1 aChristoffels, Vincent, M1 aIsaacs, Aaron1 aSamani, Nilesh, J1 ade Bakker, Paul, I W uhttps://chs-nhlbi.org/node/7262