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RESEARCH PRODUCT
Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.
Richard A. JensenDenis RybinJaakko TuomilehtoReedik MägiInga ProkopenkoInga ProkopenkoJeffrey R. O'connellMarcus E. KleberHan ChenHan ChenGeoffrey A. WalfordAllan LinnenbergAnke TönjesFrancis S. CollinsSonsoles MorcilloGemma Rojo-martínezKenneth RiceJose C. FlorezLeif GroopLeif GroopManuel Serrano-ríosJosée DupuisJosée DupuisAlisa K. ManningPeter KovacsTorben JørgensenTorben JørgensenGraciela E. DelgadoAlena StančákováHans-ulrich HäringClaudia LangenbergJoshua P. LewisNorbert StefanMarkku LaaksoTorben HansenBruce M. PsatyBruce M. PsatyJian'an LuanMichael StumvollMark O. GoodarziRobert A. ScottOluf PedersenChing-ti LiuMichael N. WeedonMichael BoehnkeUlf SmithDavid S. SiscovickDavid S. SiscovickAaron LeongWeijia XieJames B. MeigsClaes LandenvallClaes LandenvallAnne U. JacksonJoseph M. ZmudaMary L. BiggsJerome I. RotterFederico SoriguerWinfried MärzWinfried MärzWinfried MärzZhongyang ZhangMay E. MontasserArturo Corbatón-anchueloJ M Gómez-zumaqueroGünther SilbernagelKristine FærchKaren L. MohlkeHeikki A. KoistinenHeikki A. KoistinenHeikki A. KoistinenYii-der Ida ChenJaeyoung HongGracia María Martín-núñezMaría Teresa Martínez-larradEmil V. R. AppelNiels GrarupHarald StaigerJohanna KuusistoLars LindNicholas J. WarehamAndreas FritscheStefan GustafssonAndrew P. MorrisAndrew P. MorrisRichard N. BergmanMark WalkerCecilia M. LindgrenCecilia M. LindgrenErik IngelssonErik IngelssonJorge R. KizerTimothy M. FraylingFausto Machicaosubject
0301 basic medicineMaleInsulin Receptor Substrate ProteinsEndocrinology Diabetes and MetabolismLocus (genetics)Genome-wide association studyPolymorphism Single Nucleotide03 medical and health sciencesEndocrinology & MetabolismInsulin resistanceGenotypeInternal MedicinemedicineHumansGenetic Predisposition to DiseaseGenetic associationGeneticsbusiness.industryInsulin sensitivityGenetics/Genomes/Proteomics/Metabolomics11 Medical And Health Sciencesmedicine.diseaseIRS1030104 developmental biologyProto-Oncogene Proteins c-bcl-2Chemokines CCInsulin Receptor Substrate ProteinsFemaleInsulin ResistancebusinessGenome-Wide Association Studydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-07-14 |