Walford, Geoffrey AGustafsson, StefanRybin, DenisStancakova, AlenaChen, HanLiu, Ching-TiHong, JaeyoungJensen, Richard ARice, KenMorris, Andrew PMagi, ReedikTönjes, AnkeProkopenko, IngaKleber, Marcus EDelgado, GracielaSilbernagel, GüntherJackson, Anne UAppel, Emil VGrarup, NielsLewis, Joshua PMontasser, May ELandenvall, ClaesStaiger, HaraldLuan, Jian'anFrayling, Timothy MWeedon, Michael NXie, WeijiaMorcillo, SonsolesMartinez-Larrad, Maria TeresaBiggs, Mary LChen, Yii-Der IdaCorbaton-Anchuelo, ArturoFærch, KristineGomez-Zumaquero, Juan MiguelGoodarzi, Mark OKizer, Jorge RKoistinen, Heikki ALeong, AaronLind, LarsLindgren, CeciliaMachicao, FaustoManning, Alisa KMartin-Nuñez, Gracia MariaRojo-Martinez, GemmaRotter, Jerome ISiscovick, David SZmuda, Joseph MZhang, ZhongyangSerrano-Rios, ManuelSmith, UlfSoriguer, FedericoHansen, TorbenJørgensen, Torben JLinnenberg, AllanPedersen, OlufWalker, MarkLangenberg, ClaudiaScott, Robert AWareham, Nicholas JFritsche, AndreasHäring, Hans-UlrichStefan, NorbertGroop, LeifO'Connell, Jeff RBoehnke, MichaelBergman, Richard NCollins, Francis SMohlke, Karen LTuomilehto, JaakkoMärz, WinfriedKovacs, PeterStumvoll, MichaelPsaty, Bruce MKuusisto, JohannaLaakso, MarkkuMeigs, James BDupuis, JoseeIngelsson, ErikFlorez, Jose C2023-01-252023-01-252016-07-05Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu CT, et al. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci. Diabetes. 2016 Oct;65(10):3200-11http://hdl.handle.net/10668/10268Genome-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.enInsulin ResistancePolymorphism, Single NucleotideProto-Oncogene Proteins c-bcl-2Chemokines, CCFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin Receptor Substrate Proteinsresearch article27416945Restricted Access10.2337/db16-01991939-327XPMC5033262https://europepmc.org/articles/pmc5033262?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033262/pdf