04122nas a2200841 4500008004100000022001400041245017500055210006900230260001300299300001100312490000700323520169700330653001002027653001602037653000902053653002202062653001202084653001902096653002502115653001102140653003402151653001302185653001102198653001402209653000902223653001602232653001502248653003602263100002002299700001902319700002402338700002302362700002002385700002302405700002102428700001902449700002402468700002402492700002302516700002502539700002802564700002302592700002202615700002402637700001902661700001902680700001902699700002602718700002102744700002202765700002602787700002302813700001902836700002202855700002002877700002002897700002602917700001902943700002002962700002102982700002003003700002203023700001603045700002803061700002103089700002003110700002603130700002203156700001903178700002303197700002403220856003603244 2010 eng d a1758-535X00aA meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.0 ametaanalysis of four genomewide association studies of survival c2010 May a478-870 v653 a
BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity.
METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort.
RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage.
CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aAlleles10aCohort Studies10aConfidence Intervals10aFemale10aGenome-Wide Association Study10aGenotype10aHumans10aLongevity10aMale10aMiddle Aged10aOdds Ratio10aPolymorphism, Single Nucleotide1 aNewman, Anne, B1 aWalter, Stefan1 aLunetta, Kathryn, L1 aGarcia, Melissa, E1 aSlagboom, Eline1 aChristensen, Kaare1 aArnold, Alice, M1 aAspelund, Thor1 aAulchenko, Yurii, S1 aBenjamin, Emelia, J1 aChristiansen, Lene1 aD'Agostino, Ralph, B1 aFitzpatrick, Annette, L1 aFranceschini, Nora1 aGlazer, Nicole, L1 aGudnason, Vilmundur1 aHofman, Albert1 aKaplan, Robert1 aKarasik, David1 aKelly-Hayes, Margaret1 aKiel, Douglas, P1 aLauner, Lenore, J1 aMarciante, Kristin, D1 aMassaro, Joseph, M1 aMiljkovic, Iva1 aNalls, Michael, A1 aHernandez, Dena1 aPsaty, Bruce, M1 aRivadeneira, Fernando1 aRotter, Jerome1 aSeshadri, Sudha1 aSmith, Albert, V1 aTaylor, Kent, D1 aTiemeier, Henning1 aUh, Hae-Won1 aUitterlinden, André, G1 aVaupel, James, W1 aWalston, Jeremy1 aWestendorp, Rudi, G J1 aHarris, Tamara, B1 aLumley, Thomas1 aDuijn, Cornelia, M1 aMurabito, Joanne, M uhttps://chs-nhlbi.org/node/117903421nas a2200829 4500008004100000022001400041245004600055210004200101260001300143300001600156490000700172520116200179653001001341653003801351653003401389653001301423653001101436653001401447100001901461700001601480700002301496700002301519700002201542700001801564700002401582700002101606700002001627700002301647700001701670700001201687700001801699700002401717700001901741700002101760700002101781700001801802700002401820700002001844700002201864700002301886700001901909700001901928700002101947700001901968700002001987700002202007700002002029700002202049700002202071700002302093700002002116700002002136700002202156700002002178700002602198700002102224700002002245700002002265700002502285700002502310700002902335700002202364700002002386700002402406700001902430700001702449700002402466700002002490700002202510700002302532856003602555 2011 eng d a1558-149700aA genome-wide association study of aging.0 agenomewide association study of aging c2011 Nov a2109.e15-280 v323 aHuman longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.
10aAging10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHumans10aLongevity1 aWalter, Stefan1 aAtzmon, Gil1 aDemerath, Ellen, W1 aGarcia, Melissa, E1 aKaplan, Robert, C1 aKumari, Meena1 aLunetta, Kathryn, L1 aMilaneschi, Yuri1 aTanaka, Toshiko1 aTranah, Gregory, J1 aVölker, Uwe1 aYu, Lei1 aArnold, Alice1 aBenjamin, Emelia, J1 aBiffar, Reiner1 aBuchman, Aron, S1 aBoerwinkle, Eric1 aCouper, David1 aDe Jager, Philip, L1 aEvans, Denis, A1 aHarris, Tamara, B1 aHoffmann, Wolfgang1 aHofman, Albert1 aKarasik, David1 aKiel, Douglas, P1 aKocher, Thomas1 aKuningas, Maris1 aLauner, Lenore, J1 aLohman, Kurt, K1 aLutsey, Pamela, L1 aMackenbach, Johan1 aMarciante, Kristin1 aPsaty, Bruce, M1 aReiman, Eric, M1 aRotter, Jerome, I1 aSeshadri, Sudha1 aShardell, Michelle, D1 aSmith, Albert, V1 aDuijn, Cornelia1 aWalston, Jeremy1 aZillikens, Carola, M1 aBandinelli, Stefania1 aBaumeister, Sebastian, E1 aBennett, David, A1 aFerrucci, Luigi1 aGudnason, Vilmundur1 aKivimaki, Mika1 aLiu, Yongmei1 aMurabito, Joanne, M1 aNewman, Anne, B1 aTiemeier, Henning1 aFranceschini, Nora uhttps://chs-nhlbi.org/node/130707748nas a2202497 4500008004100000022001400041245011400055210006900169260001600238300001000254490000700264520075000271653001601021653001801037653002501055653001601080653001501096653002301111653003201134653004001166653002601206653001101232653001701243653003401260653001101294653001301305653001401318653003601332653001301368100001901381700002101400700002301421700001601444700002101460700001901481700001901500700001701519700001901536700001901555700001601574700002301590700002801613700002401641700001701665700002401682700002001706700001801726700002101744700002601765700001801791700001901809700001801828700002501846700001901871700002501890700002501915700002501940700001801965700002101983700002402004700001802028700002002046700002402066700002002090700002502110700001802135700002402153700001702177700001702194700001802211700001902229700001802248700002702266700002502293700001802318700002402336700002002360700002302380700002402403700001902427700002002446700002002466700002102486700002302507700002102530700002202551700001902573700002602592700001402618700001902632700002402651700001602675700002202691700002102713700001902734700002002753700002602773700002302799700001902822700002402841700001802865700002102883700001802904700002102922700001602943700001602959700001702975700002102992700002203013700001703035700002003052700002303072700002703095700001903122700002403141700003003165700002303195700002203218700002203240700001803262700002003280700001703300700002003317700002003337700003103357700001903388700002103407700002003428700002303448700002403471700002003495700002103515700001903536700002103555700002003576700002303596700001903619700002203638700001603660700001703676700002103693700002003714700002203734700002303756700002003779700002003799700002103819700001903840700002703859700002303886700002103909700002603930700001603956700001903972700002103991700002104012700002604033700001404059700001804073700002004091700002204111700002304133700002204156700002404178700002304202700002204225700002004247700002504267700002304292700002104315700003404336700002304370700002104393700003004414700002004444700003104464700002204495700001604517700002504533700001904558700002104577700002304598700002104621700002004642700002304662700002404685700002204709700001704731700002104748700002204769700002104791700002504812700001904837700002004856700001804876700002404894700002004918700002104938700002704959700002804986700001705014700002805031700002305059700001905082700001705101700002405118700002105142700002405163710002705187856003605214 2012 eng d a1546-171800aMeta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.0 aMetaanalyses identify 13 loci associated with age at menopause a c2012 Jan 22 a260-80 v443 aTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
10aAge Factors10aDNA Helicases10aDNA Polymerase gamma10aDNA Primase10aDNA Repair10aDNA Repair Enzymes10aDNA-Directed DNA Polymerase10aEuropean Continental Ancestry Group10aExodeoxyribonucleases10aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aImmunity10aMenopause10aPolymorphism, Single Nucleotide10aProteins1 aStolk, Lisette1 aPerry, John, R B1 aChasman, Daniel, I1 aHe, Chunyan1 aMangino, Massimo1 aSulem, Patrick1 aBarbalic, Maja1 aBroer, Linda1 aByrne, Enda, M1 aErnst, Florian1 aEsko, Tõnu1 aFranceschini, Nora1 aGudbjartsson, Daniel, F1 aHottenga, Jouke-Jan1 aKraft, Peter1 aMcArdle, Patrick, F1 aPorcu, Eleonora1 aShin, So-Youn1 aSmith, Albert, V1 avan Wingerden, Sophie1 aZhai, Guangju1 aZhuang, Wei, V1 aAlbrecht, Eva1 aAlizadeh, Behrooz, Z1 aAspelund, Thor1 aBandinelli, Stefania1 aLauc, Lovorka, Barac1 aBeckmann, Jacques, S1 aBoban, Mladen1 aBoerwinkle, Eric1 aBroekmans, Frank, J1 aBurri, Andrea1 aCampbell, Harry1 aChanock, Stephen, J1 aChen, Constance1 aCornelis, Marilyn, C1 aCorre, Tanguy1 aCoviello, Andrea, D1 aD'Adamo, Pio1 aDavies, Gail1 ade Faire, Ulf1 aGeus, Eco, J C1 aDeary, Ian, J1 aDedoussis, George, V Z1 aDeloukas, Panagiotis1 aEbrahim, Shah1 aEiriksdottir, Gudny1 aEmilsson, Valur1 aEriksson, Johan, G1 aFauser, Bart, C J M1 aFerreli, Liana1 aFerrucci, Luigi1 aFischer, Krista1 aFolsom, Aaron, R1 aGarcia, Melissa, E1 aGasparini, Paolo1 aGieger, Christian1 aGlazer, Nicole1 aGrobbee, Diederick, E1 aHall, Per1 aHaller, Toomas1 aHankinson, Susan, E1 aHass, Merli1 aHayward, Caroline1 aHeath, Andrew, C1 aHofman, Albert1 aIngelsson, Erik1 aJanssens, Cecile, J W1 aJohnson, Andrew, D1 aKarasik, David1 aKardia, Sharon, L R1 aKeyzer, Jules1 aKiel, Douglas, P1 aKolcic, Ivana1 aKutalik, Zoltán1 aLahti, Jari1 aLai, Sandra1 aLaisk, Triin1 aLaven, Joop, S E1 aLawlor, Debbie, A1 aLiu, Jianjun1 aLopez, Lorna, M1 aLouwers, Yvonne, V1 aMagnusson, Patrik, K E1 aMarongiu, Mara1 aMartin, Nicholas, G1 aKlaric, Irena, Martinovic1 aMasciullo, Corrado1 aMcKnight, Barbara1 aMedland, Sarah, E1 aMelzer, David1 aMooser, Vincent1 aNavarro, Pau1 aNewman, Anne, B1 aNyholt, Dale, R1 aOnland-Moret, Charlotte, N1 aPalotie, Aarno1 aParé, Guillaume1 aParker, Alex, N1 aPedersen, Nancy, L1 aPeeters, Petra, H M1 aPistis, Giorgio1 aPlump, Andrew, S1 aPolasek, Ozren1 aPop, Victor, J M1 aPsaty, Bruce, M1 aRäikkönen, Katri1 aRehnberg, Emil1 aRotter, Jerome, I1 aRudan, Igor1 aSala, Cinzia1 aSalumets, Andres1 aScuteri, Angelo1 aSingleton, Andrew1 aSmith, Jennifer, A1 aSnieder, Harold1 aSoranzo, Nicole1 aStacey, Simon, N1 aStarr, John, M1 aStathopoulou, Maria, G1 aStirrups, Kathleen1 aStolk, Ronald, P1 aStyrkarsdottir, Unnur1 aSun, Yan, V1 aTenesa, Albert1 aThorand, Barbara1 aToniolo, Daniela1 aTryggvadottir, Laufey1 aTsui, Kim1 aUlivi, Sheila1 avan Dam, Rob, M1 aSchouw, Yvonne, T1 avan Gils, Carla, H1 avan Nierop, Peter1 aVink, Jacqueline, M1 aVisscher, Peter, M1 aVoorhuis, Marlies1 aWaeber, Gérard1 aWallaschofski, Henri1 aWichmann, Erich, H1 aWiden, Elisabeth1 avan Gent, Colette, J M Wijnan1 aWillemsen, Gonneke1 aWilson, James, F1 aWolffenbuttel, Bruce, H R1 aWright, Alan, F1 aYerges-Armstrong, Laura, M1 aZemunik, Tatijana1 aZgaga, Lina1 aZillikens, Carola, M1 aZygmunt, Marek1 aArnold, Alice, M1 aBoomsma, Dorret, I1 aBuring, Julie, E1 aCrisponi, Laura1 aDemerath, Ellen, W1 aGudnason, Vilmundur1 aHarris, Tamara, B1 aHu, Frank, B1 aHunter, David, J1 aLauner, Lenore, J1 aMetspalu, Andres1 aMontgomery, Grant, W1 aOostra, Ben, A1 aRidker, Paul, M1 aSanna, Serena1 aSchlessinger, David1 aSpector, Tim, D1 aStefansson, Kari1 aStreeten, Elizabeth, A1 aThorsteinsdottir, Unnur1 aUda, Manuela1 aUitterlinden, André, G1 aDuijn, Cornelia, M1 aVölzke, Henry1 aMurray, Anna1 aMurabito, Joanne, M1 aVisser, Jenny, A1 aLunetta, Kathryn, L1 aLifeLines Cohort Study uhttps://chs-nhlbi.org/node/136003769nas a2200937 4500008004100000022001400041245009400055210006900149260001600218300001200234490000700246520111800253653002201371653001601393653002301409653004001432653001101472653001701483653002201500653003401522653001101556653001401567653001801581100002501599700001801624700001801642700002501660700002101685700001801706700002301724700002301747700002201770700001201792700002001804700002301824700002201847700002201869700002001891700002801911700002201939700002201961700002001983700002302003700001802026700002802044700001802072700002202090700002202112700001902134700002002153700001702173700002302190700002302213700002202236700002102258700001802279700002202297700002202319700002202341700002002363700002202383700001402405700001502419700002202434700002202456700002402478700002402502700002402526700001702550700002202567700001702589700002102606700002402627700002302651700002502674700002302699700002402722700002402746700002502770856003602795 2014 eng d a1460-208300aMeta-analysis of loci associated with age at natural menopause in African-American women.0 aMetaanalysis of loci associated with age at natural menopause in c2014 Jun 15 a3327-420 v233 aAge at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.
10aAfrican Americans10aAge Factors10aChromosomes, Human10aEuropean Continental Ancestry Group10aFemale10aGenetic Loci10aGenetic Variation10aGenome-Wide Association Study10aHumans10aMenopause10aUnited States1 aChen, Christina, T L1 aLiu, Ching-Ti1 aChen, Gary, K1 aAndrews, Jeanette, S1 aArnold, Alice, M1 aDreyfus, Jill1 aFranceschini, Nora1 aGarcia, Melissa, E1 aKerr, Kathleen, F1 aLi, Guo1 aLohman, Kurt, K1 aMusani, Solomon, K1 aNalls, Michael, A1 aRaffel, Leslie, J1 aSmith, Jennifer1 aAmbrosone, Christine, B1 aBandera, Elisa, V1 aBernstein, Leslie1 aBritton, Angela1 aBrzyski, Robert, G1 aCappola, Anne1 aCarlson, Christopher, S1 aCouper, David1 aDeming, Sandra, L1 aGoodarzi, Mark, O1 aHeiss, Gerardo1 aJohn, Esther, M1 aLu, Xiaoning1 aLe Marchand, Loïc1 aMarciante, Kristin1 aMcKnight, Barbara1 aMillikan, Robert1 aNock, Nora, L1 aOlshan, Andrew, F1 aPress, Michael, F1 aVaiyda, Dhananjay1 aWoods, Nancy, F1 aTaylor, Herman, A1 aZhao, Wei1 aZheng, Wei1 aEvans, Michele, K1 aHarris, Tamara, B1 aHenderson, Brian, E1 aKardia, Sharon, L R1 aKooperberg, Charles1 aLiu, Yongmei1 aMosley, Thomas, H1 aPsaty, Bruce1 aWellons, Melissa1 aWindham, Beverly, G1 aZonderman, Alan, B1 aCupples, Adrienne, L1 aDemerath, Ellen, W1 aHaiman, Christopher1 aMurabito, Joanne, M1 aRajkovic, Aleksandar uhttps://chs-nhlbi.org/node/655205848nas a2201069 4500008004100000022001400041245018600055210006900241260001300310300001200323490000800335520268400343653001803027653001903045653003203064653003803096653003403134653001103168653001803179653002003197653001203217653002303229653002803252653000903280653001803289653001603307653003603323653001703359100002203376700002003398700002703418700002403445700002003469700002403489700003203513700002003545700002803565700002303593700001603616700002003632700002903652700001903681700003203700700002503732700001803757700002003775700001903795700002303814700002103837700002203858700002003880700002303900700002403923700002103947700002103968700002603989700002104015700002004036700002104056700001804077700002504095700001704120700002004137700002304157700002404180700002204204700001904226700001604245700002004261700002104281700002404302700002104326700001704347700002104364700002804385700002004413700002104433700002004454700002504474700002304499700002004522700002104542700001904563700002304582700002504605700002104630700002204651700002504673700002004698700002404718856003604742 2015 eng d a1938-320700aConsumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians.0 aConsumption of meat is associated with higher fasting glucose an c2015 Nov a1266-780 v1023 aBACKGROUND: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.
OBJECTIVE: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.
DESIGN: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations.
RESULTS: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance.
CONCLUSION: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).
10aBlood Glucose10aCohort Studies10aGenetic Association Studies10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aHyperglycemia10aHyperinsulinism10aInsulin10aInsulin Resistance10aInsulin-Secreting Cells10aMeat10aMeat Products10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk Factors1 aFretts, Amanda, M1 aFollis, Jack, L1 aNettleton, Jennifer, A1 aLemaitre, Rozenn, N1 aNgwa, Julius, S1 aWojczynski, Mary, K1 aKalafati, Ioanna, Panagiota1 aVarga, Tibor, V1 aFrazier-Wood, Alexis, C1 aHouston, Denise, K1 aLahti, Jari1 aEricson, Ulrika1 avan den Hooven, Edith, H1 aMikkilä, Vera1 ade Jong, Jessica, C Kiefte-1 aMozaffarian, Dariush1 aRice, Kenneth1 aRenstrom, Frida1 aNorth, Kari, E1 aMcKeown, Nicola, M1 aFeitosa, Mary, F1 aKanoni, Stavroula1 aSmith, Caren, E1 aGarcia, Melissa, E1 aTiainen, Anna-Maija1 aSonestedt, Emily1 aManichaikul, Ani1 avan Rooij, Frank, J A1 aDimitriou, Maria1 aRaitakari, Olli1 aPankow, James, S1 aDjoussé, Luc1 aProvince, Michael, A1 aHu, Frank, B1 aLai, Chao-Qiang1 aKeller, Margaux, F1 aPerälä, Mia-Maria1 aRotter, Jerome, I1 aHofman, Albert1 aGraff, Misa1 aKähönen, Mika1 aMukamal, Kenneth1 aJohansson, Ingegerd1 aOrdovas, Jose, M1 aLiu, Yongmei1 aMännistö, Satu1 aUitterlinden, André, G1 aDeloukas, Panos1 aSeppälä, Ilkka1 aPsaty, Bruce, M1 aCupples, Adrienne, L1 aBorecki, Ingrid, B1 aFranks, Paul, W1 aArnett, Donna, K1 aNalls, Mike, A1 aEriksson, Johan, G1 aOrho-Melander, Marju1 aFranco, Oscar, H1 aLehtimäki, Terho1 aDedoussis, George, V1 aMeigs, James, B1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/684404127nas a2200877 4500008004100000022001400041245007800055210006900133260001300202300001000215490000700225520166400232653000901896653002201905653002201927653002801949653001901977653001101996653002802007653003502035653003402070653001102104653001402115653000902129653001602138653003602154653002702190100001702217700002102234700001802255700002102273700002102294700002402315700002202339700002302361700002102384700002002405700001202425700002102437700001902458700002402477700002402501700002402525700002002549700002302569700001902592700002202611700002402633700002102657700001902678700002002697700001802717700002002735700002602755700002202781700002002803700002202823700002202845700002802867700001402895700002502909700002202934700002002956700002402976700002203000700001903022700002203041700002103063700002003084700002303104700001903127700002003146700002303166700002403189856003603213 2015 eng d a1758-535X00aGWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.0 aGWAS of longevity in CHARGE consortium confirms APOE and FOXO3 c c2015 Jan a110-80 v703 aBACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.
METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.
RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).
CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.
10aAged10aAged, 80 and over10aApolipoproteins E10aCell Adhesion Molecules10aCohort Studies10aFemale10aForkhead Box Protein O310aForkhead Transcription Factors10aGenome-Wide Association Study10aHumans10aLongevity10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aReceptors, Kainic Acid1 aBroer, Linda1 aBuchman, Aron, S1 aDeelen, Joris1 aEvans, Daniel, S1 aFaul, Jessica, D1 aLunetta, Kathryn, L1 aSebastiani, Paola1 aSmith, Jennifer, A1 aSmith, Albert, V1 aTanaka, Toshiko1 aYu, Lei1 aArnold, Alice, M1 aAspelund, Thor1 aBenjamin, Emelia, J1 aDe Jager, Philip, L1 aEirkisdottir, Gudny1 aEvans, Denis, A1 aGarcia, Melissa, E1 aHofman, Albert1 aKaplan, Robert, C1 aKardia, Sharon, L R1 aKiel, Douglas, P1 aOostra, Ben, A1 aOrwoll, Eric, S1 aParimi, Neeta1 aPsaty, Bruce, M1 aRivadeneira, Fernando1 aRotter, Jerome, I1 aSeshadri, Sudha1 aSingleton, Andrew1 aTiemeier, Henning1 aUitterlinden, André, G1 aZhao, Wei1 aBandinelli, Stefania1 aBennett, David, A1 aFerrucci, Luigi1 aGudnason, Vilmundur1 aHarris, Tamara, B1 aKarasik, David1 aLauner, Lenore, J1 aPerls, Thomas, T1 aSlagboom, Eline1 aTranah, Gregory, J1 aWeir, David, R1 aNewman, Anne, B1 aDuijn, Cornelia, M1 aMurabito, Joanne, M uhttps://chs-nhlbi.org/node/655009013nas a2202797 4500008004100000022001400041245011400055210006900169260000900238300000900247490000600256520115900262653003901421653001801460653003001478653004001508653001001548653001201558653003201570653001701602653003801619653002201657653003701679653002601716653001101742653001201753653001801765653004401783653003601827100002101863700001901884700002101903700001601924700002301940700002301963700001801986700002502004700002402029700002202053700002002075700001502095700002502110700001302135700001802148700003102166700001802197700002102215700001102236700002602247700002502273700002002298700001902318700001702337700002302354700002002377700002302397700002302420700001702443700001602460700001802476700002602494700002102520700002002541700001202561700002002573700002102593700002402614700001902638700002502657700002502682700002302707700002102730700002102751700002202772700002302794700002502817700002002842700002002862700002302882700001602905700002402921700001402945700002302959700002502982700002103007700002303028700002203051700001903073700001703092700001903109700002003128700001903148700002203167700001903189700002003208700002403228700002203252700002503274700002303299700002203322700002303344700002403367700001503391700002003406700002003426700002303446700001403469700002103483700001703504700001803521700002303539700002303562700002503585700002303610700002403633700001903657700002403676700001903700700002203719700002003741700001403761700001803775700001703793700001703810700001603827700001703843700002503860700002103885700002203906700002203928700002003950700002203970700002003992700002704012700001704039700002304056700002104079700002004100700001904120700002604139700001804165700001904183700002104202700002004223700001404243700002004257700002004277700002704297700002304324700002004347700002804367700001804395700002304413700002304436700002704459700001704486700002104503700002704524700001804551700001904569700001904588700002104607700001904628700002004647700002504667700001904692700002004711700002204731700002004753700002304773700002004796700002004816700002104836700002104857700002204878700001704900700002604917700001904943700002404962700002204986700002005008700002005028700002105048700002005069700002205089700002405111700002005135700002205155700002605177700002205203700001905225700002405244700002405268700002205292700001705314700001905331700003005350700002305380700002505403700002105428700001905449700002505468700002105493700002005514700001605534700002505550700002005575700002805595700001705623700001805640700001805658700002405676700001905700700002305719700002305742700001905765700002005784700001905804700002305823700002505846700002405871700002105895700002005916700002005936700002005956700002105976700002505997700002406022700001906046700002206065700002006087700002106107700002206128710002906150856003606179 2015 eng d a2041-172300aLow-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.0 aLowfrequency and rare exome chip variants associate with fasting c2015 a58970 v63 aFasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
10aAfrican Continental Ancestry Group10aBlood Glucose10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aExome10aFasting10aGenetic Association Studies10aGenetic Loci10aGenetic Predisposition to Disease10aGenetic Variation10aGlucagon-Like Peptide-1 Receptor10aGlucose-6-Phosphatase10aHumans10aInsulin10aMutation Rate10aOligonucleotide Array Sequence Analysis10aPolymorphism, Single Nucleotide1 aWessel, Jennifer1 aChu, Audrey, Y1 aWillems, Sara, M1 aWang, Shuai1 aYaghootkar, Hanieh1 aBrody, Jennifer, A1 aDauriz, Marco1 aHivert, Marie-France1 aRaghavan, Sridharan1 aLipovich, Leonard1 aHidalgo, Bertha1 aFox, Keolu1 aHuffman, Jennifer, E1 aAn, Ping1 aLu, Yingchang1 aRasmussen-Torvik, Laura, J1 aGrarup, Niels1 aEhm, Margaret, G1 aLi, Li1 aBaldridge, Abigail, S1 aStančáková, Alena1 aAbrol, Ravinder1 aBesse, Céline1 aBoland, Anne1 aBork-Jensen, Jette1 aFornage, Myriam1 aFreitag, Daniel, F1 aGarcia, Melissa, E1 aGuo, Xiuqing1 aHara, Kazuo1 aIsaacs, Aaron1 aJakobsdottir, Johanna1 aLange, Leslie, A1 aLayton, Jill, C1 aLi, Man1 aZhao, Jing, Hua1 aMeidtner, Karina1 aMorrison, Alanna, C1 aNalls, Mike, A1 aPeters, Marjolein, J1 aSabater-Lleal, Maria1 aSchurmann, Claudia1 aSilveira, Angela1 aSmith, Albert, V1 aSoutham, Lorraine1 aStoiber, Marcus, H1 aStrawbridge, Rona, J1 aTaylor, Kent, D1 aVarga, Tibor, V1 aAllin, Kristine, H1 aAmin, Najaf1 aAponte, Jennifer, L1 aAung, Tin1 aBarbieri, Caterina1 aBihlmeyer, Nathan, A1 aBoehnke, Michael1 aBombieri, Cristina1 aBowden, Donald, W1 aBurns, Sean, M1 aChen, Yuning1 aChen, Yii-DerI1 aCheng, Ching-Yu1 aCorrea, Adolfo1 aCzajkowski, Jacek1 aDehghan, Abbas1 aEhret, Georg, B1 aEiriksdottir, Gudny1 aEscher, Stefan, A1 aFarmaki, Aliki-Eleni1 aFrånberg, Mattias1 aGambaro, Giovanni1 aGiulianini, Franco1 aGoddard, William, A1 aGoel, Anuj1 aGottesman, Omri1 aGrove, Megan, L1 aGustafsson, Stefan1 aHai, Yang1 aHallmans, Göran1 aHeo, Jiyoung1 aHoffmann, Per1 aIkram, Mohammad, K1 aJensen, Richard, A1 aJørgensen, Marit, E1 aJørgensen, Torben1 aKaraleftheri, Maria1 aKhor, Chiea, C1 aKirkpatrick, Andrea1 aKraja, Aldi, T1 aKuusisto, Johanna1 aLange, Ethan, M1 aLee, I, T1 aLee, Wen-Jane1 aLeong, Aaron1 aLiao, Jiemin1 aLiu, Chunyu1 aLiu, Yongmei1 aLindgren, Cecilia, M1 aLinneberg, Allan1 aMalerba, Giovanni1 aMamakou, Vasiliki1 aMarouli, Eirini1 aMaruthur, Nisa, M1 aMatchan, Angela1 aMcKean-Cowdin, Roberta1 aMcLeod, Olga1 aMetcalf, Ginger, A1 aMohlke, Karen, L1 aMuzny, Donna, M1 aNtalla, Ioanna1 aPalmer, Nicholette, D1 aPasko, Dorota1 aPeter, Andreas1 aRayner, Nigel, W1 aRenstrom, Frida1 aRice, Ken1 aSala, Cinzia, F1 aSennblad, Bengt1 aSerafetinidis, Ioannis1 aSmith, Jennifer, A1 aSoranzo, Nicole1 aSpeliotes, Elizabeth, K1 aStahl, Eli, A1 aStirrups, Kathleen1 aTentolouris, Nikos1 aThanopoulou, Anastasia1 aTorres, Mina1 aTraglia, Michela1 aTsafantakis, Emmanouil1 aJavad, Sundas1 aYanek, Lisa, R1 aZengini, Eleni1 aBecker, Diane, M1 aBis, Joshua, C1 aBrown, James, B1 aCupples, Adrienne, L1 aHansen, Torben1 aIngelsson, Erik1 aKarter, Andrew, J1 aLorenzo, Carlos1 aMathias, Rasika, A1 aNorris, Jill, M1 aPeloso, Gina, M1 aSheu, Wayne, H-H1 aToniolo, Daniela1 aVaidya, Dhananjay1 aVarma, Rohit1 aWagenknecht, Lynne, E1 aBoeing, Heiner1 aBottinger, Erwin, P1 aDedoussis, George1 aDeloukas, Panos1 aFerrannini, Ele1 aFranco, Oscar, H1 aFranks, Paul, W1 aGibbs, Richard, A1 aGudnason, Vilmundur1 aHamsten, Anders1 aHarris, Tamara, B1 aHattersley, Andrew, T1 aHayward, Caroline1 aHofman, Albert1 aJansson, Jan-Håkan1 aLangenberg, Claudia1 aLauner, Lenore, J1 aLevy, Daniel1 aOostra, Ben, A1 aO'Donnell, Christopher, J1 aO'Rahilly, Stephen1 aPadmanabhan, Sandosh1 aPankow, James, S1 aPolasek, Ozren1 aProvince, Michael, A1 aRich, Stephen, S1 aRidker, Paul, M1 aRudan, Igor1 aSchulze, Matthias, B1 aSmith, Blair, H1 aUitterlinden, André, G1 aWalker, Mark1 aWatkins, Hugh1 aWong, Tien, Y1 aZeggini, Eleftheria1 aLaakso, Markku1 aBorecki, Ingrid, B1 aChasman, Daniel, I1 aPedersen, Oluf1 aPsaty, Bruce, M1 aTai, Shyong, E1 aDuijn, Cornelia, M1 aWareham, Nicholas, J1 aWaterworth, Dawn, M1 aBoerwinkle, Eric1 aKao, Linda, W H1 aFlorez, Jose, C1 aLoos, Ruth, J F1 aWilson, James, G1 aFrayling, Timothy, M1 aSiscovick, David, S1 aDupuis, Josée1 aRotter, Jerome, I1 aMeigs, James, B1 aScott, Robert, A1 aGoodarzi, Mark, O1 aEPIC-InterAct Consortium uhttps://chs-nhlbi.org/node/668604458nas a2200937 4500008004100000022001400041245009600055210006900151260001300220300001200233490000700245520181500252100002102067700002002088700001902108700001602127700001802143700002002161700002302181700002102204700002602225700001702251700002102268700002202289700001702311700002402328700002102352700002102373700002302394700002202417700001202439700001902451700002102470700002202491700002402513700002002537700002102557700002302578700002702601700002402628700001902652700001902671700002002690700001902710700002202729700001702751700001702768700002602785700002202811700002802833700001902861700002102880700002302901700002802924700001702952700001902969700001902988700002003007700001403027700002403041700002103065700002203086700002403108700001803132700002003150700002203170700002403192700001903216700002803235700002003263700002003283700002403303700002603327700001803353700002503371700002003396700002303416700002103439700002403460856003603484 2016 eng d a1474-972600aGWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.0 aGWAS analysis of handgrip and lower body strength in older adult c2016 Oct a792-8000 v153 aDecline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10(-8) ) and 39 suggestive (P-value< 5 × 10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.
1 aMatteini, Amy, M1 aTanaka, Toshiko1 aKarasik, David1 aAtzmon, Gil1 aChou, Wen-Chi1 aEicher, John, D1 aJohnson, Andrew, D1 aArnold, Alice, M1 aCallisaya, Michele, L1 aDavies, Gail1 aEvans, Daniel, S1 aHoltfreter, Birte1 aLohman, Kurt1 aLunetta, Kathryn, L1 aMangino, Massimo1 aSmith, Albert, V1 aSmith, Jennifer, A1 aTeumer, Alexander1 aYu, Lei1 aArking, Dan, E1 aBuchman, Aron, S1 aChibinik, Lori, B1 aDe Jager, Philip, L1 aEvans, Denis, A1 aFaul, Jessica, D1 aGarcia, Melissa, E1 aGillham-Nasenya, Irina1 aGudnason, Vilmundur1 aHofman, Albert1 aHsu, Yi-Hsiang1 aIttermann, Till1 aLahousse, Lies1 aLiewald, David, C1 aLiu, Yongmei1 aLopez, Lorna1 aRivadeneira, Fernando1 aRotter, Jerome, I1 aSiggeirsdottir, Kristin1 aStarr, John, M1 aThomson, Russell1 aTranah, Gregory, J1 aUitterlinden, André, G1 aVölker, Uwe1 aVölzke, Henry1 aWeir, David, R1 aYaffe, Kristine1 aZhao, Wei1 aZhuang, Wei, Vivian1 aZmuda, Joseph, M1 aBennett, David, A1 aCummings, Steven, R1 aDeary, Ian, J1 aFerrucci, Luigi1 aHarris, Tamara, B1 aKardia, Sharon, L R1 aKocher, Thomas1 aKritchevsky, Stephen, B1 aPsaty, Bruce, M1 aSeshadri, Sudha1 aSpector, Timothy, D1 aSrikanth, Velandai, K1 aWindham, Gwen1 aZillikens, Carola, M1 aNewman, Anne, B1 aWalston, Jeremy, D1 aKiel, Douglas, P1 aMurabito, Joanne, M uhttps://chs-nhlbi.org/node/714203298nas a2200793 4500008004100000022001400041245008800055210006900143260001300212300001300225490000700238520090200245100002601147700002501173700001901198700002201217700002201239700002101261700002001282700001401302700002101316700002101337700002401358700002301382700002101405700001601426700001801442700003001460700002101490700002601511700002001537700001801557700002001575700002301595700002201618700002001640700002001660700002001680700002101700700002101721700002401742700002301766700002001789700002401809700002101833700002001854700001701874700002801891700002001919700002201939700001901961700003001980700002802010700002202038700001902060700001802079700002002097700002802117700002102145700002002166700002002186700002302206700002402229700002302253710007602276710004502352710007102397856003602468 2016 eng d a1553-740400aRare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.0 aRare Functional Variant in TM2D3 is Associated with LateOnset Al c2016 Oct ae10063270 v123 aWe performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.
1 aJakobsdottir, Johanna1 avan der Lee, Sven, J1 aBis, Joshua, C1 aChouraki, Vincent1 aLi-Kroeger, David1 aYamamoto, Shinya1 aGrove, Megan, L1 aNaj, Adam1 aVronskaya, Maria1 aSalazar, Jose, L1 aDeStefano, Anita, L1 aBrody, Jennifer, A1 aSmith, Albert, V1 aAmin, Najaf1 aSims, Rebecca1 aIbrahim-Verbaas, Carla, A1 aChoi, Seung-Hoan1 aSatizabal, Claudia, L1 aLopez, Oscar, L1 aBeiser, Alexa1 aIkram, Arfan, M1 aGarcia, Melissa, E1 aHayward, Caroline1 aVarga, Tibor, V1 aRipatti, Samuli1 aFranks, Paul, W1 aHallmans, Göran1 aRolandsson, Olov1 aJansson, Jan-Håkon1 aPorteous, David, J1 aSalomaa, Veikko1 aEiriksdottir, Gudny1 aRice, Kenneth, M1 aBellen, Hugo, J1 aLevy, Daniel1 aUitterlinden, André, G1 aEmilsson, Valur1 aRotter, Jerome, I1 aAspelund, Thor1 aO'Donnell, Christopher, J1 aFitzpatrick, Annette, L1 aLauner, Lenore, J1 aHofman, Albert1 aSan Wang, Li-1 aWilliams, Julie1 aSchellenberg, Gerard, D1 aBoerwinkle, Eric1 aPsaty, Bruce, M1 aSeshadri, Sudha1 aShulman, Joshua, M1 aGudnason, Vilmundur1 aDuijn, Cornelia, M1 aCohorts for Heart and Aging Research in Genomic Epidemiology Consortium1 aAlzheimer’s Disease Genetic Consortium1 aGenetic and Environmental Risk in Alzheimer’s Disease consortium uhttps://chs-nhlbi.org/node/726009668nas a2203061 4500008004100000022001400041245007500055210006900130260001300199300001400212490000700226520116500233653002801398653003001426653001001456653003201466653003801498653002201536653001301558653001101571653001101582653002501593653001401618653001701632100002001649700002001669700001501689700002501704700001501729700002001744700002101764700001801785700001601803700003101819700002201850700003001872700002401902700002901926700001801955700001701973700002801990700001702018700001902035700001902054700002102073700002102094700002302115700002402138700002102162700001802183700002002201700002302221700002202244700002302266700001702289700002202306700001902328700002402347700001902371700002102390700002102411700002502432700002302457700001702480700001802497700002202515700002102537700002102558700002402579700002002603700002402623700001602647700002502663700002102688700002002709700002002729700001402749700002002763700002002783700002502803700002502828700002202853700002302875700002102898700002202919700001302941700002302954700002202977700002302999700002203022700002103044700001803065700001603083700002003099700002403119700001903143700002203162700002203184700002403206700002303230700002203253700001403275700002003289700002003309700002103329700002603350700002703376700002003403700002503423700001903448700002503467700002103492700002203513700001903535700001503554700001903569700001803588700002503606700002203631700002403653700002003677700002203697700001903719700001603738700002403754700001903778700002203797700002303819700002403842700001603866700002103882700002003903700001803923700001803941700001803959700002303977700002104000700002204021700002404043700002004067700002504087700002004112700002004132700001904152700002104171700002204192700002404214700002104238700003004259700002404289700002104313700002204334700002104356700002804377700002104405700001904426700002904445700002504474700002204499700002204521700002504543700002304568700001804591700002304609700001904632700001904651700002004670700002404690700002004714700001904734700001804753700002004771700002104791700001804812700002104830700002204851700002004873700002004893700002104913700002004934700001904954700002304973700001804996700002205014700001605036700002005052700002205072700001805094700001905112700002205131700002105153700001705174700002305191700002605214700001705240700002805257700002105285700002105306700002005327700002605347700002205373700002405395700002805419700001905447700002605466700002105492700002405513700002605537700002305563700001705586700001805603700001405621700002405635700002005659700002005679700002005699700002305719700002605742700002705768700001805795700002005813700001905833700002605852700001405878700002105892700002105913700002005934700002205954700002105976700002105997700002306018700001306041700002306054700001706077700002406094700001406118700001906132700001806151700001506169700001406184700001706198700002806215700002406243700001706267700002206284700001906306700002206325700002006347700002006367700002306387700002206410710003406432710002906466710002406495710002006519710003106539856003606570 2017 eng d a1546-171800aExome-wide association study of plasma lipids in >300,000 individuals.0 aExomewide association study of plasma lipids in 300000 individua c2017 Dec a1758-17660 v493 aWe screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
10aCoronary Artery Disease10aDiabetes Mellitus, Type 210aExome10aGenetic Association Studies10aGenetic Predisposition to Disease10aGenetic Variation10aGenotype10aHumans10aLipids10aMacular Degeneration10aPhenotype10aRisk Factors1 aLiu, Dajiang, J1 aPeloso, Gina, M1 aYu, Haojie1 aButterworth, Adam, S1 aWang, Xiao1 aMahajan, Anubha1 aSaleheen, Danish1 aEmdin, Connor1 aAlam, Dewan1 aAlves, Alexessander, Couto1 aAmouyel, Philippe1 aDi Angelantonio, Emanuele1 aArveiler, Dominique1 aAssimes, Themistocles, L1 aAuer, Paul, L1 aBaber, Usman1 aBallantyne, Christie, M1 aBang, Lia, E1 aBenn, Marianne1 aBis, Joshua, C1 aBoehnke, Michael1 aBoerwinkle, Eric1 aBork-Jensen, Jette1 aBottinger, Erwin, P1 aBrandslund, Ivan1 aBrown, Morris1 aBusonero, Fabio1 aCaulfield, Mark, J1 aChambers, John, C1 aChasman, Daniel, I1 aChen, Eugene1 aChen, Yii-Der Ida1 aChowdhury, Raj1 aChristensen, Cramer1 aChu, Audrey, Y1 aConnell, John, M1 aCucca, Francesco1 aCupples, Adrienne, L1 aDamrauer, Scott, M1 aDavies, Gail1 aDeary, Ian, J1 aDedoussis, George1 aDenny, Joshua, C1 aDominiczak, Anna1 aDubé, Marie-Pierre1 aEbeling, Tapani1 aEiriksdottir, Gudny1 aEsko, Tõnu1 aFarmaki, Aliki-Eleni1 aFeitosa, Mary, F1 aFerrario, Marco1 aFerrieres, Jean1 aFord, Ian1 aFornage, Myriam1 aFranks, Paul, W1 aFrayling, Timothy, M1 aFrikke-Schmidt, Ruth1 aFritsche, Lars, G1 aFrossard, Philippe1 aFuster, Valentin1 aGanesh, Santhi, K1 aGao, Wei1 aGarcia, Melissa, E1 aGieger, Christian1 aGiulianini, Franco1 aGoodarzi, Mark, O1 aGrallert, Harald1 aGrarup, Niels1 aGroop, Leif1 aGrove, Megan, L1 aGudnason, Vilmundur1 aHansen, Torben1 aHarris, Tamara, B1 aHayward, Caroline1 aHirschhorn, Joel, N1 aHolmen, Oddgeir, L1 aHuffman, Jennifer1 aHuo, Yong1 aHveem, Kristian1 aJabeen, Sehrish1 aJackson, Anne, U1 aJakobsdottir, Johanna1 aJarvelin, Marjo-Riitta1 aJensen, Gorm, B1 aJørgensen, Marit, E1 aJukema, Wouter1 aJustesen, Johanne, M1 aKamstrup, Pia, R1 aKanoni, Stavroula1 aKarpe, Fredrik1 aKee, Frank1 aKhera, Amit, V1 aKlarin, Derek1 aKoistinen, Heikki, A1 aKooner, Jaspal, S1 aKooperberg, Charles1 aKuulasmaa, Kari1 aKuusisto, Johanna1 aLaakso, Markku1 aLakka, Timo1 aLangenberg, Claudia1 aLangsted, Anne1 aLauner, Lenore, J1 aLauritzen, Torsten1 aLiewald, David, C M1 aLin, Li, An1 aLinneberg, Allan1 aLoos, Ruth, J F1 aLu, Yingchang1 aLu, Xiangfeng1 aMägi, Reedik1 aMälarstig, Anders1 aManichaikul, Ani1 aManning, Alisa, K1 aMäntyselkä, Pekka1 aMarouli, Eirini1 aMasca, Nicholas, G D1 aMaschio, Andrea1 aMeigs, James, B1 aMelander, Olle1 aMetspalu, Andres1 aMorris, Andrew, P1 aMorrison, Alanna, C1 aMulas, Antonella1 aMüller-Nurasyid, Martina1 aMunroe, Patricia, B1 aNeville, Matt, J1 aNielsen, Jonas, B1 aNielsen, Sune, F1 aNordestgaard, Børge, G1 aOrdovas, Jose, M1 aMehran, Roxana1 aO'Donnell, Christoper, J1 aOrho-Melander, Marju1 aMolony, Cliona, M1 aMuntendam, Pieter1 aPadmanabhan, Sandosh1 aPalmer, Colin, N A1 aPasko, Dorota1 aPatel, Aniruddh, P1 aPedersen, Oluf1 aPerola, Markus1 aPeters, Annette1 aPisinger, Charlotta1 aPistis, Giorgio1 aPolasek, Ozren1 aPoulter, Neil1 aPsaty, Bruce, M1 aRader, Daniel, J1 aRasheed, Asif1 aRauramaa, Rainer1 aReilly, Dermot, F1 aReiner, Alex, P1 aRenstrom, Frida1 aRich, Stephen, S1 aRidker, Paul, M1 aRioux, John, D1 aRobertson, Neil, R1 aRoden, Dan, M1 aRotter, Jerome, I1 aRudan, Igor1 aSalomaa, Veikko1 aSamani, Nilesh, J1 aSanna, Serena1 aSattar, Naveed1 aSchmidt, Ellen, M1 aScott, Robert, A1 aSever, Peter1 aSevilla, Raquel, S1 aShaffer, Christian, M1 aSim, Xueling1 aSivapalaratnam, Suthesh1 aSmall, Kerrin, S1 aSmith, Albert, V1 aSmith, Blair, H1 aSomayajula, Sangeetha1 aSoutham, Lorraine1 aSpector, Timothy, D1 aSpeliotes, Elizabeth, K1 aStarr, John, M1 aStirrups, Kathleen, E1 aStitziel, Nathan1 aStrauch, Konstantin1 aStringham, Heather, M1 aSurendran, Praveen1 aTada, Hayato1 aTall, Alan, R1 aTang, Hua1 aTardif, Jean-Claude1 aTaylor, Kent, D1 aTrompet, Stella1 aTsao, Philip, S1 aTuomilehto, Jaakko1 aTybjaerg-Hansen, Anne1 avan Zuydam, Natalie, R1 aVarbo, Anette1 aVarga, Tibor, V1 aVirtamo, Jarmo1 aWaldenberger, Melanie1 aWang, Nan1 aWareham, Nick, J1 aWarren, Helen, R1 aWeeke, Peter, E1 aWeinstock, Joshua1 aWessel, Jennifer1 aWilson, James, G1 aWilson, Peter, W F1 aXu, Ming1 aYaghootkar, Hanieh1 aYoung, Robin1 aZeggini, Eleftheria1 aZhang, He1 aZheng, Neil, S1 aZhang, Weihua1 aZhang, Yan1 aZhou, Wei1 aZhou, Yanhua1 aZoledziewska, Magdalena1 aHowson, Joanna, M M1 aDanesh, John1 aMcCarthy, Mark, I1 aCowan, Chad, A1 aAbecasis, Goncalo1 aDeloukas, Panos1 aMusunuru, Kiran1 aWiller, Cristen, J1 aKathiresan, Sekar1 aCharge Diabetes Working Group1 aEPIC-InterAct Consortium1 aEPIC-CVD Consortium1 aGOLD Consortium1 aVA Million Veteran Program uhttps://chs-nhlbi.org/node/757304016nas a2200865 4500008004100000022001400041245009800055210006900153260001600222520147500238100002001713700002001733700002201753700002001775700002201795700002201817700002801839700002401867700002101891700001901912700003201931700001701963700002801980700002402008700001602032700002202048700001902070700001902089700002002108700001902128700002102147700002002168700002302188700001902211700002002230700001402250700002302264700001902287700002502306700002102331700002102352700002402373700002902397700002502426700002502451700002302476700002502499700002502524700002102549700002402570700002202594700003202616700002002648700002202668700001902690700002302709700002202732700002902754700002502783700002302808700001902831700001702850700002102867700001902888700002202907700002202929700002802951700002602979700002103005700001803026700002403044700002503068700002103093856003603114 2017 eng d a1613-413300aGenome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.0 aGenomeWide Interactions with Dairy Intake for Body Mass Index in c2017 Sep 213 aSCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.
METHODS AND RESULTS: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10-8) such that each serving of low-fat dairy was associated with 0.225 kg m-2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure.
CONCLUSION: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
1 aSmith, Caren, E1 aFollis, Jack, L1 aDashti, Hassan, S1 aTanaka, Toshiko1 aGraff, Mariaelisa1 aFretts, Amanda, M1 aKilpeläinen, Tuomas, O1 aWojczynski, Mary, K1 aRichardson, Kris1 aNalls, Mike, A1 aSchulz, Christina-Alexandra1 aLiu, Yongmei1 aFrazier-Wood, Alexis, C1 avan Eekelen, Esther1 aWang, Carol1 ade Vries, Paul, S1 aMikkilä, Vera1 aRohde, Rebecca1 aPsaty, Bruce, M1 aHansen, Torben1 aFeitosa, Mary, F1 aLai, Chao-Qiang1 aHouston, Denise, K1 aFerruci, Luigi1 aEricson, Ulrika1 aWang, Zhe1 ade Mutsert, Renée1 aOddy, Wendy, H1 ade Jonge, Ester, A L1 aSeppälä, Ilkka1 aJustice, Anne, E1 aLemaitre, Rozenn, N1 aSørensen, Thorkild, I A1 aProvince, Michael, A1 aParnell, Laurence, D1 aGarcia, Melissa, E1 aBandinelli, Stefania1 aOrho-Melander, Marju1 aRich, Stephen, S1 aRosendaal, Frits, R1 aPennell, Craig, E1 ade Jong, Jessica, C Kiefte-1 aKähönen, Mika1 aYoung, Kristin, L1 aPedersen, Oluf1 aAslibekyan, Stella1 aRotter, Jerome, I1 aMook-Kanamori, Dennis, O1 aZillikens, Carola, M1 aRaitakari, Olli, T1 aNorth, Kari, E1 aOvervad, Kim1 aArnett, Donna, K1 aHofman, Albert1 aLehtimäki, Terho1 aTjønneland, Anne1 aUitterlinden, André, G1 aRivadeneira, Fernando1 aFranco, Oscar, H1 aGerman, Bruce1 aSiscovick, David, S1 aCupples, Adrienne, L1 aOrdovas, Jose, M uhttps://chs-nhlbi.org/node/758817687nas a2205785 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2017 eng d a1546-171800aRare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.0 aRare coding variants in PLCG2 ABI3 and TREM2 implicate microglia c2017 Sep a1373-13840 v493 aWe identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
10aAdaptor Proteins, Signal Transducing10aAlzheimer Disease10aAmino Acid Sequence10aCase-Control Studies10aExome10aGene Expression Profiling10aGene Frequency10aGenetic Predisposition to Disease10aGenotype10aHumans10aImmunity, Innate10aLinkage Disequilibrium10aMembrane Glycoproteins10aMicroglia10aOdds Ratio10aPhospholipase C gamma10aPolymorphism, Single Nucleotide10aProtein Interaction Maps10aReceptors, Immunologic10aSequence Homology, Amino Acid1 aSims, Rebecca1 avan der Lee, Sven, J1 aNaj, Adam, C1 aBellenguez, Céline1 aBadarinarayan, Nandini1 aJakobsdottir, Johanna1 aKunkle, Brian, W1 aBoland, Anne1 aRaybould, Rachel1 aBis, Joshua, C1 aMartin, Eden, R1 aGrenier-Boley, Benjamin1 aHeilmann-Heimbach, Stefanie1 aChouraki, Vincent1 aKuzma, Amanda, B1 aSleegers, Kristel1 aVronskaya, Maria1 aRuiz, Agustin1 aGraham, Robert, R1 aOlaso, Robert1 aHoffmann, Per1 aGrove, Megan, L1 aVardarajan, Badri, N1 aHiltunen, Mikko1 aNöthen, Markus, M1 aWhite, Charles, C1 aHamilton-Nelson, Kara, L1 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aMann, David1 aTsolaki, Magda1 aClarimon, Jordi1 aSussams, Rebecca1 aLovestone, Simon1 aO'Donovan, Michael, C1 aOwen, Michael, J1 aBehrens, Timothy, W1 aMead, Simon1 aGoate, Alison, M1 aUitterlinden, André, G1 aHolmes, Clive1 aCruchaga, Carlos1 aIngelsson, Martin1 aBennett, David, A1 aPowell, John1 aGolde, Todd, E1 aGraff, Caroline1 aDe Jager, Philip, L1 aMorgan, Kevin1 aErtekin-Taner, Nilufer1 aCombarros, Onofre1 aPsaty, Bruce, M1 aPassmore, Peter1 aYounkin, Steven, G1 aBerr, Claudine1 aGudnason, Vilmundur1 aRujescu, Dan1 aDickson, Dennis, W1 aDartigues, Jean-François1 aDeStefano, Anita, L1 aOrtega-Cubero, Sara1 aHakonarson, Hakon1 aCampion, Dominique1 aBoada, Merce1 aKauwe, John, Keoni1 aFarrer, Lindsay, A1 aVan Broeckhoven, Christine1 aIkram, Arfan, M1 aJones, Lesley1 aHaines, Jonathan, L1 aTzourio, Christophe1 aLauner, Lenore, J1 aEscott-Price, Valentina1 aMayeux, Richard1 aDeleuze, Jean-Francois1 aAmin, Najaf1 aHolmans, Peter, A1 aPericak-Vance, Margaret, A1 aAmouyel, Philippe1 aDuijn, Cornelia, M1 aRamirez, Alfredo1 aSan Wang, Li-1 aLambert, Jean-Charles1 aSeshadri, Sudha1 aWilliams, Julie1 aSchellenberg, Gerard, D1 aARUK Consortium1 aGERAD/PERADES, CHARGE, ADGC, EADI uhttps://chs-nhlbi.org/node/758717696nas a2205797 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2019 eng d a1546-171800aGenetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.0 aGenetic metaanalysis of diagnosed Alzheimers disease identifies c2019 Mar a414-4300 v513 aRisk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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aLambert, Jean-Charles1 aPericak-Vance, Margaret, A1 aAlzheimer Disease Genetics Consortium (ADGC),1 aEuropean Alzheimer’s Disease Initiative (EADI),1 aCohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE),1 aGenetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), uhttps://chs-nhlbi.org/node/797705314nas a2201501 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2020 eng d a1939-327X00aGenetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.0 aGenetic Studies of Leptin Concentrations Implicate Leptin in the c2020 Sep 113 aLeptin influences food intake by informing the brain about the status of body fat stores. Rare mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in , and , and one intergenic variant near The missense variant Val94Met (rs17151919) in was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10, n=3,901). Using analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting leptin regulates early adiposity.
1 aYaghootkar, Hanieh1 aZhang, Yiying1 aSpracklen, Cassandra, N1 aKaraderi, Tugce1 aHuang, Lam, Opal1 aBradfield, Jonathan1 aSchurmann, Claudia1 aFine, Rebecca, S1 aPreuss, Michael, H1 aKutalik, Zoltán1 aWittemans, Laura, Bl1 aLu, Yingchang1 aMetz, Sophia1 aWillems, Sara, M1 aLi-Gao, Ruifang1 aGrarup, Niels1 aWang, Shuai1 aMolnos, Sophie1 aSandoval-Zárate, América, A1 aNalls, Mike, A1 aLange, Leslie, A1 aHaesser, Jeffrey1 aGuo, Xiuqing1 aLyytikäinen, Leo-Pekka1 aFeitosa, Mary, F1 aSitlani, Colleen, M1 aVenturini, Cristina1 aMahajan, Anubha1 aKacprowski, Tim1 aWang, Carol, A1 aChasman, Daniel, I1 aAmin, Najaf1 aBroer, Linda1 aRobertson, Neil1 aYoung, Kristin, L1 aAllison, Matthew1 aAuer, Paul, L1 aBlüher, Matthias1 aBorja, Judith, B1 aBork-Jensen, Jette1 aCarrasquilla, Germán, D1 aChristofidou, Paraskevi1 aDemirkan, Ayse1 aDoege, Claudia, A1 aGarcia, Melissa, E1 aGraff, Mariaelisa1 aGuo, Kaiying1 aHakonarson, Hakon1 aHong, Jaeyoung1 aChen, Yii-Der, Ida1 aJackson, Rebecca1 aJakupović, Hermina1 aJousilahti, Pekka1 aJustice, Anne, E1 aKähönen, Mika1 aKizer, Jorge, R1 aKriebel, Jennifer1 aLeDuc, Charles, A1 aLi, Jin1 aLind, Lars1 aLuan, Jian'an1 aMackey, David1 aMangino, Massimo1 aMännistö, Satu1 aCarli, Jayne, F Martin1 aMedina-Gómez, Carolina1 aMook-Kanamori, Dennis, O1 aMorris, Andrew, P1 ade Mutsert, Renée1 aNauck, Matthias1 aNedeljkovic, Ivana1 aPennell, Craig, E1 aPradhan, Arund, D1 aPsaty, Bruce, M1 aRaitakari, Olli, T1 aScott, Robert, A1 aSkaaby, Tea1 aStrauch, Konstantin1 aTaylor, Kent, D1 aTeumer, Alexander1 aUitterlinden, André, G1 aWu, Ying1 aYao, Jie1 aWalker, Mark1 aNorth, Kari, E1 aKovacs, Peter1 aIkram, Arfan, M1 aDuijn, Cornelia, M1 aRidker, Paul, M1 aLye, Stephen1 aHomuth, Georg1 aIngelsson, Erik1 aSpector, Tim, D1 aMcKnight, Barbara1 aProvince, Michael, A1 aLehtimäki, Terho1 aAdair, Linda, S1 aRotter, Jerome, I1 aReiner, Alexander, P1 aWilson, James, G1 aHarris, Tamara, B1 aRipatti, Samuli1 aGrallert, Harald1 aMeigs, James, B1 aSalomaa, Veikko1 aHansen, Torben1 avan Dijk, Ko, Willems1 aWareham, Nicholas, J1 aGrant, Struan, Fa1 aLangenberg, Claudia1 aFrayling, Timothy, M1 aLindgren, Cecilia, M1 aMohlke, Karen, L1 aLeibel, Rudolph, L1 aLoos, Ruth, Jf1 aKilpeläinen, Tuomas, O uhttps://chs-nhlbi.org/node/8491