04555nas a2201081 4500008004100000022001400041245014800055210006900203260001300272300001200285490000700297520142500304100002501729700002301754700001701777700002501794700001401819700001801833700001901851700002301870700001401893700002201907700001801929700001801947700002101965700002201986700002202008700002602030700002102056700001902077700001802096700002102114700002202135700002202157700002002179700001802199700002502217700002302242700001602265700002302281700003602304700001902340700002202359700003002381700002102411700003502432700002202467700002002489700002502509700001702534700001502551700002202566700002102588700002202609700003602631700002602667700002202693700002402715700002102739700002102760700002602781700001502807700002302822700001902845700002602864700002202890700001902912700001702931700002402948700002102972700002502993700002203018700002503040700002003065700001603085700002303101700002103124700002403145700002403169700002103193700002303214700002003237700001803257700002203275700002003297700002203317700001903339700002003358700001903378700002003397700002003417856003603437 2016 eng d a1939-327X00aGenome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.0 aGenomeWide Association Study of the Modified Stumvoll Insulin Se c2016 Oct a3200-110 v653 a
Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.
1 aWalford, Geoffrey, A1 aGustafsson, Stefan1 aRybin, Denis1 aStančáková, Alena1 aChen, Han1 aLiu, Ching-Ti1 aHong, Jaeyoung1 aJensen, Richard, A1 aRice, Ken1 aMorris, Andrew, P1 aMägi, Reedik1 aTönjes, Anke1 aProkopenko, Inga1 aKleber, Marcus, E1 aDelgado, Graciela1 aSilbernagel, Günther1 aJackson, Anne, U1 aAppel, Emil, V1 aGrarup, Niels1 aLewis, Joshua, P1 aMontasser, May, E1 aLandenvall, Claes1 aStaiger, Harald1 aLuan, Jian'an1 aFrayling, Timothy, M1 aWeedon, Michael, N1 aXie, Weijia1 aMorcillo, Sonsoles1 aMartínez-Larrad, María Teresa1 aBiggs, Mary, L1 aChen, Yii-Der Ida1 aCorbaton-Anchuelo, Arturo1 aFærch, Kristine1 aGómez-Zumaquero, Juan, Miguel1 aGoodarzi, Mark, O1 aKizer, Jorge, R1 aKoistinen, Heikki, A1 aLeong, Aaron1 aLind, Lars1 aLindgren, Cecilia1 aMachicao, Fausto1 aManning, Alisa, K1 aMartín-Núñez, Gracia, María1 aRojo-Martínez, Gemma1 aRotter, Jerome, I1 aSiscovick, David, S1 aZmuda, Joseph, M1 aZhang, Zhongyang1 aSerrano-Ríos, Manuel1 aSmith, Ulf1 aSoriguer, Federico1 aHansen, Torben1 aJørgensen, Torben, J1 aLinnenberg, Allan1 aPedersen, Oluf1 aWalker, Mark1 aLangenberg, Claudia1 aScott, Robert, A1 aWareham, Nicholas, J1 aFritsche, Andreas1 aHäring, Hans-Ulrich1 aStefan, Norbert1 aGroop, Leif1 aO'Connell, Jeff, R1 aBoehnke, Michael1 aBergman, Richard, N1 aCollins, Francis, S1 aMohlke, Karen, L1 aTuomilehto, Jaakko1 aMärz, Winfried1 aKovacs, Peter1 aStumvoll, Michael1 aPsaty, Bruce, M1 aKuusisto, Johanna1 aLaakso, Markku1 aMeigs, James, B1 aDupuis, Josée1 aIngelsson, Erik1 aFlorez, Jose, C uhttps://chs-nhlbi.org/node/7167