Willems, Sara MSara MWillemsNg, Natasha H JNatasha H JNgFernandez, JuanJuanFernandezFine, Rebecca SRebecca SFineWheeler, EleanorEleanorWheelerWessel, JenniferJenniferWesselKitajima, HidetoshiHidetoshiKitajimaMarenne, GaelleGaelleMarenneSim, XuelingXuelingSimYaghootkar, HaniehHaniehYaghootkarWang, ShuaiShuaiWangChen, SaiSaiChenChen, YuningYuningChenChen, Yii-Der IdaYii-Der IdaChenGrarup, NielsNielsGrarupLi-Gao, RuifangRuifangLi-GaoVarga, Tibor VTibor VVargaAsimit, Jennifer LJennifer LAsimitFeng, ShuangShuangFengStrawbridge, Rona JRona JStrawbridgeKleinbrink, Erica LErica LKleinbrinkAhluwalia, Tarunveer STarunveer SAhluwaliaAn, PingPingAnAppel, Emil VEmil VAppelArking, Dan EDan EArkingAuvinen, JuhaJuhaAuvinenBielak, Lawrence FLawrence FBielakBihlmeyer, Nathan ANathan ABihlmeyerBork-Jensen, JetteJetteBork-JensenBrody, Jennifer AJennifer ABrodyCampbell, ArchieArchieCampbellChu, Audrey YAudrey YChuDavies, GailGailDaviesDemirkan, AyseAyseDemirkanFloyd, James SJames SFloydGiulianini, 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JakobJakobStokholmStrauch, KonstantinKonstantinStrauchTai, E-ShyongE-ShyongTaiTaylor, Kent DKent DTaylorThuesen, Betina HBetina HThuesenTönjes, AnkeAnkeTönjesTsafantakis, EmmanouilEmmanouilTsafantakisTuomi, TiinamaijaTiinamaijaTuomiTuomilehto, JaakkoJaakkoTuomilehtoUusitupa, MattiMattiUusitupaVääräsmäki, MarjaMarjaVääräsmäkiVaartjes, IloncaIloncaVaartjesZoledziewska, MagdalenaMagdalenaZoledziewskaAbecasis, GoncaloGoncaloAbecasisBalkau, BeverleyBeverleyBalkauBisgaard, HansHansBisgaardBlakemore, Alexandra IAlexandra IBlakemoreBlüher, MatthiasMatthiasBlüherBoeing, HeinerHeinerBoeingBoerwinkle, EricEricBoerwinkleBønnelykke, KlausKlausBønnelykkeBottinger, Erwin PErwin PBottingerCaulfield, Mark JMark JCaulfieldChambers, John CJohn CChambersChasman, Daniel IDaniel IChasmanCheng, Ching-YuChing-YuChengCollins, Francis SFrancis SCollinsCoresh, JosefJosefCoreshCucca, FrancescoFrancescoCuccade Borst, Gert JGert Jde BorstDeary, Ian JIan JDearyDedoussis, GeorgeGeorgeDedoussisDeloukas, 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APalmerPasterkamp, GerardGerardPasterkampPedersen, OlufOlufPedersenPeyser, Patricia APatricia APeyserPolasek, OzrenOzrenPolasekPorteous, DavidDavidPorteousProvince, Michael AMichael AProvincePsaty, Bruce MBruce MPsatyRauramaa, RainerRainerRauramaaRidker, Paul MPaul MRidkerRolandsson, OlovOlovRolandssonRorsman, PatrikPatrikRorsmanRosendaal, Frits RFrits RRosendaalRudan, IgorIgorRudanSalomaa, VeikkoVeikkoSalomaaSchulze, Matthias BMatthias BSchulzeSladek, RobertRobertSladekSmith, Blair HBlair HSmithSpector, Timothy DTimothy DSpectorStarr, John MJohn MStarrStumvoll, MichaelMichaelStumvollvan Duijn, Cornelia MCornelia Mvan DuijnWalker, MarkMarkWalkerWareham, Nick JNick JWarehamWeir, David RDavid RWeirWilson, James GJames GWilsonWong, Tien YinTien YinWongZeggini, EleftheriaEleftheriaZegginiZonderman, Alan BAlan BZondermanRotter, Jerome IJerome IRotterMorris, Andrew PAndrew PMorrisBoehnke, MichaelMichaelBoehnkeFlorez, Jose CJose CFlorezMcCarthy, Mark IMark IMcCarthyMeigs, James BJames BMeigsMahajan, AnubhaAnubhaMahajanScott, Robert ARobert AScottGloyn, Anna LAnna LGloynBarroso, InêsInêsBarroso2024-11-062024-11-062023https://boris-portal.unibe.ch/handle/20.500.12422/103437Background Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.Methods To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses.Results Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology.Conclusions Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.eneffector genesexome chipgenetic discoveryglycaemic traitssummary statistics resources600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.48620/760863928006310.12688/wellcomeopenres.18754.1