Wessel, JenniferChu, Audrey Y.Willems, Sara M.Wang, ShuaiYaghootkar, HaniehBrody, Jennifer A.Dauriz, MarcoHivert, Marie-FranceRaghavan, SridharanLipovich, LeonardHidalgo, BerthaFox, KeoluHuffman, Jennifer E.An, PingLu, YingchangRasmussen-Torvik, Laura J.Grarup, NielsEhm, Margaret G.Li, LiBaldridge, Abigail S.Stančáková, AlenaAbrol, RavinderBesse, CélineBoland, AnneBork-Jensen, JetteFornage, MyriamFreitag, Daniel F.Garcia, Melissa E.Guo, XiuqingHara, KazuoIsaacs, AaronJakobsdottir, JohannaLange, Leslie A.Layton, Jill C.Li, ManHua Zhao, JingMeidtner, KarinaMorrison, Alanna C.Nalls, Mike A.Peters, Marjolein J.Sabater-Lleal, MariaSchurmann, ClaudiaSilveira, AngelaSmith, Albert V.Southam, LorraineStoiber, Marcus H.Strawbridge, Rona J.Taylor, Kent D.Varga, Tibor V.Allin, Kristine H.Amin, NajafAponte, Jennifer L.Aung, TinBarbieri, CaterinaBihlmeyer, Nathan A.Boehnke, MichaelBombieri, CristinaBowden, Donald W.Burns, Sean M.Chen, YuningChen, Yii-DerICheng, Ching-YuCorrea, AdolfoCzajkowski, JacekDehghan, AbbasEhret, Georg B.Eiriksdottir, GudnyEscher, Stefan A.Farmaki, Aliki-EleniFrånberg, MattiasGambaro, GiovanniGiulianini, FrancoGoddard, William A.Goel, AnujGottesman, OmriGrove, Megan L.Gustafsson, StefanHai, YangHallmans, GöranHeo, JiyoungHoffmann, PerIkram, Mohammad K.Jensen, Richard A.Jørgensen, Marit E.Jørgensen, TorbenKaraleftheri, MariaKhor, Chiea C.Kirkpatrick, AndreaKraja, Aldi T.Kuusisto, JohannaLange, Ethan M.Lee, I. T.Lee, Wen-JaneLeong, AaronLiao, JieminLiu, ChunyuLiu, YongmeiLindgren, Cecilia M.Linneberg, AllanMalerba, GiovanniMamakou, VasilikiMarouli, EiriniMaruthur, Nisa M.Matchan, AngelaMcKean-Cowdin, RobertaMcLeod, OlgaMetcalf, Ginger A.Mohlke, Karen L.Muzny, Donna M.Ntalla, IoannaPalmer, Nicholette D.Pasko, DorotaPeter, AndreasRayner, Nigel W.Renström, FridaRice, KenSala, Cinzia F.Sennblad, BengtSerafetinidis, IoannisSmith, Jennifer A.Soranzo, NicoleSpeliotes, Elizabeth K.Stahl, Eli A.Stirrups, KathleenTentolouris, NikosThanopoulou, AnastasiaTorres, MinaTraglia, MichelaTsafantakis, EmmanouilJavad, SundasYanek, Lisa R.Zengini, EleniBecker, Diane M.Bis, Joshua C.Brown, James B.Adrienne Cupples, L.Hansen, TorbenIngelsson, ErikKarter, Andrew J.Lorenzo, CarlosMathias, Rasika A.Norris, Jill M.Peloso, Gina M.Sheu, Wayne H.-H.Toniolo, DanielaVaidya, DhananjayVarma, RohitWagenknecht, Lynne E.Boeing, HeinerBottinger, Erwin P.Dedoussis, GeorgeDeloukas, PanosFerrannini, EleFranco, Oscar H.Franks, Paul W.Gibbs, Richard A.Gudnason, VilmundurHamsten, AndersHarris, Tamara B.Hattersley, Andrew T.Hayward, CarolineHofman, AlbertJansson, Jan-HåkanLangenberg, ClaudiaLauner, Lenore J.Levy, DanielOostra, Ben A.O'Donnell, Christopher J.O'Rahilly, StephenPadmanabhan, SandoshPankow, James S.Polasek, OzrenProvince, Michael A.Rich, Stephen S.Ridker, Paul M.Rudan, IgorSchulze, Matthias B.Smith, Blair H.Uitterlinden, André G.Walker, MarkWatkins, HughWong, Tien Y.Zeggini, EleftheriaLaakso, MarkkuBorecki, Ingrid B.Chasman, Daniel I.Pedersen, OlufPsaty, Bruce M.Shyong Tai, E.van Duijn, Cornelia M.Wareham, Nicholas J.Waterworth, Dawn M.Boerwinkle, EricLinda Kao, W. H.Florez, Jose C.Loos, Ruth J. F.Wilson, James G.Frayling, Timothy M.Siscovick, David S.Dupuis, JoséeRotter, Jerome I.Meigs, James B.Scott, Robert A.Goodarzi, Mark O.2016-03-182016-03-182015-01-29Wessel, J., Chu, A. Y., Willems, S. M., Wang, S., Yaghootkar, H., Brody, J. A., … Goodarzi, M. O. (2015). Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nature Communications, 6, 5897. http://doi.org/10.1038/ncomms68972041-1723https://hdl.handle.net/1805/8945Fasting ​glucose and ​insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in ​GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=−0.09±0.01 mmol l−1, P=3.4 × 10−12), T2D risk (OR[95%CI]=0.86[0.76–0.96], P=0.010), early ​insulin secretion (β=−0.07±0.035 pmolinsulin mmolglucose−1, P=0.048), but higher 2-h ​glucose (β=0.16±0.05 mmol l−1, P=4.3 × 10−4). We identify a gene-based association with FG at ​G6PC2 (pSKAT=6.8 × 10−6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ​ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l−1, P=1.3 × 10−8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.en-USAttribution 3.0 United StatesBlood GlucosemetabolismDiabetes Mellitus, Type 2geneticsExomeFastingbloodGenetic Predisposition to DiseaseMutation RateOligonucleotide Array Sequence AnalysisArticle