04872nas a2201453 4500008004100000022001400041245010900055210006900164260001600233300000900249490000600258520072200264653002100986653003401007653001101041653005101052653002101103653003601124100001801160700002001178700002501198700002301223700001601246700002101262700002301283700001701306700002501323700002401348700002201372700002201394700001901416700001701435700002001452700001201472700002101484700002101505700002801526700002301554700002501577700002001602700002401622700001401646700002601660700002001686700001901706700002401725700001701749700001801766700001901784700002201803700001801825700002201843700001901865700002601884700002101910700002501931700002401956700001801980700002501998700002202023700002102045700001702066700002402083700001602107700001602123700001902139700002202158700001602180700001902196700001902215700001802234700002302252700001902275700002102294700001802315700002102333700002002354700003002374700002702404700001602431700002202447700001802469700001602487700001702503700002302520700001602543700002202559700002102581700002602602700002002628700002502648700002802673700002402701700002302725700002202748700001902770700002302789700002302812700002202835700002002857700002302877700002802900700001902928700002602947700002002973700002102993700002003014700002403034700001703058700002103075700002803096700002203124700002203146700002003168700002303188700002403211700002203235700001903257700002203276700001903298700002303317710004203340856003603382 2014 eng d a2041-172300aPharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.0 aPharmacogenetic metaanalysis of genomewide association studies o c2014 Oct 28 a50680 v53 a
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
10aCholesterol, LDL10aGenome-Wide Association Study10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aPharmacogenetics10aPolymorphism, Single Nucleotide1 aPostmus, Iris1 aTrompet, Stella1 aDeshmukh, Harshal, A1 aBarnes, Michael, R1 aLi, Xiaohui1 aWarren, Helen, R1 aChasman, Daniel, I1 aZhou, Kaixin1 aArsenault, Benoit, J1 aDonnelly, Louise, A1 aWiggins, Kerri, L1 aAvery, Christy, L1 aGriffin, Paula1 aFeng, QiPing1 aTaylor, Kent, D1 aLi, Guo1 aEvans, Daniel, S1 aSmith, Albert, V1 ade Keyser, Catherine, E1 aJohnson, Andrew, D1 ade Craen, Anton, J M1 aStott, David, J1 aBuckley, Brendan, M1 aFord, Ian1 aWestendorp, Rudi, G J1 aSlagboom, Eline1 aSattar, Naveed1 aMunroe, Patricia, B1 aSever, Peter1 aPoulter, Neil1 aStanton, Alice1 aShields, Denis, C1 aO'Brien, Eoin1 aShaw-Hawkins, Sue1 aChen, Y-D, Ida1 aNickerson, Deborah, A1 aSmith, Joshua, D1 aDubé, Marie, Pierre1 aBoekholdt, Matthijs1 aHovingh, Kees1 aKastelein, John, J P1 aMcKeigue, Paul, M1 aBetteridge, John1 aNeil, Andrew1 aDurrington, Paul, N1 aDoney, Alex1 aCarr, Fiona1 aMorris, Andrew1 aMcCarthy, Mark, I1 aGroop, Leif1 aAhlqvist, Emma1 aBis, Joshua, C1 aRice, Kenneth1 aSmith, Nicholas, L1 aLumley, Thomas1 aWhitsel, Eric, A1 aStürmer, Til1 aBoerwinkle, Eric1 aNgwa, Julius, S1 aO'Donnell, Christopher, J1 aVasan, Ramachandran, S1 aWei, Wei-Qi1 aWilke, Russell, A1 aLiu, Ching-Ti1 aSun, Fangui1 aGuo, Xiuqing1 aHeckbert, Susan, R1 aPost, Wendy1 aSotoodehnia, Nona1 aArnold, Alice, M1 aStafford, Jeanette, M1 aDing, Jingzhong1 aHerrington, David, M1 aKritchevsky, Stephen, B1 aEiriksdottir, Gudny1 aLauner, Leonore, J1 aHarris, Tamara, B1 aChu, Audrey, Y1 aGiulianini, Franco1 aMacFadyen, Jean, G1 aBarratt, Bryan, J1 aNyberg, Fredrik1 aStricker, Bruno, H1 aUitterlinden, André, G1 aHofman, Albert1 aRivadeneira, Fernando1 aEmilsson, Valur1 aFranco, Oscar, H1 aRidker, Paul, M1 aGudnason, Vilmundur1 aLiu, Yongmei1 aDenny, Joshua, C1 aBallantyne, Christie, M1 aRotter, Jerome, I1 aCupples, Adrienne1 aPsaty, Bruce, M1 aPalmer, Colin, N A1 aTardif, Jean-Claude1 aColhoun, Helen, M1 aHitman, Graham1 aKrauss, Ronald, M1 aJukema, Wouter1 aCaulfield, Mark, J1 aWelcome Trust Case Control Consortium uhttps://chs-nhlbi.org/node/659104450nas a2201069 4500008004100000022001400041245015100055210006900206260001300275300001200288490000700300520139200307100002101699700001901720700002301739700002301762700001601785700002001801700001901821700002101840700002501861700002301886700002101909700001801930700002201948700001701970700002701987700002202014700001702036700002102053700002002074700002002094700001502114700001402129700001702143700001602160700001702176700001702193700002102210700001702231700001302248700002002261700002102281700001902302700002302321700001402344700002102358700001902379700002302398700001802421700001802439700003202457700002702489700001702516700002202533700001602555700001902571700002302590700002102613700001902634700002102653700002202674700001802696700002002714700002202734700001702756700002002773700001702793700001902810700002102829700001902850700002002869700001902889700002402908700002302932700001802955700002202973700002102995700002103016700002503037700001903062700002303081700001803104700002403122700001803146700002203164700002203186700002003208700001803228710009803246856003603344 2019 eng d a1939-327X00aMultiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.0 aMultiethnic GenomeWide Association Study of Diabetic Retinopathy c2019 Feb a441-4560 v683 aTo identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a value <1 × 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like () was associated with DR in European discovery cohorts ( = 2.1 × 10), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.
1 aPollack, Samuela1 aIgo, Robert, P1 aJensen, Richard, A1 aChristiansen, Mark1 aLi, Xiaohui1 aCheng, Ching-Yu1 aC Y Ng, Maggie1 aSmith, Albert, V1 aRossin, Elizabeth, J1 aSegrè, Ayellet, V1 aDavoudi, Samaneh1 aTan, Gavin, S1 aChen, Yii-Der Ida1 aKuo, Jane, Z1 aDimitrov, Latchezar, M1 aStanwyck, Lynn, K1 aMeng, Weihua1 aHosseini, Mohsen1 aImamura, Minako1 aNousome, Darryl1 aKim, Jihye1 aHai, Yang1 aJia, Yucheng1 aAhn, Jeeyun1 aLeong, Aaron1 aShah, Kaanan1 aPark, Kyu, Hyung1 aGuo, Xiuqing1 aIpp, Eli1 aTaylor, Kent, D1 aAdler, Sharon, G1 aSedor, John, R1 aFreedman, Barry, I1 aLee, I-Te1 aSheu, Wayne, H-H1 aKubo, Michiaki1 aTakahashi, Atsushi1 aHadjadj, Samy1 aMarre, Michel1 aTrégouët, David-Alexandre1 aMcKean-Cowdin, Roberta1 aVarma, Rohit1 aMcCarthy, Mark, I1 aGroop, Leif1 aAhlqvist, Emma1 aLyssenko, Valeriya1 aAgardh, Elisabet1 aMorris, Andrew1 aDoney, Alex, S F1 aColhoun, Helen, M1 aToppila, Iiro1 aSandholm, Niina1 aGroop, Per-Henrik1 aMaeda, Shiro1 aHanis, Craig, L1 aPenman, Alan1 aChen, Ching, J1 aHancock, Heather1 aMitchell, Paul1 aCraig, Jamie, E1 aChew, Emily, Y1 aPaterson, Andrew, D1 aGrassi, Michael, A1 aPalmer, Colin1 aBowden, Donald, W1 aYaspan, Brian, L1 aSiscovick, David1 aCotch, Mary, Frances1 aWang, Jie, Jin1 aBurdon, Kathryn, P1 aWong, Tien, Y1 aKlein, Barbara, E K1 aKlein, Ronald1 aRotter, Jerome, I1 aIyengar, Sudha, K1 aPrice, Alkes, L1 aSobrin, Lucia1 aFamily Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group uhttps://chs-nhlbi.org/node/7990