Wessel, JenniferChu, Audrey YWillems, Sara MWang, ShuaiYaghootkar, HaniehBrody, Jennifer ADauriz, MarcoHivert, Marie-FranceRaghavan, SridharanLipovich, LeonardHidalgo, BerthaFox, KeoluHuffman, Jennifer EAn, PingLu, YingchangRasmussen-Torvik, Laura JGrarup, NielsEhm, Margaret GLi, LiBaldridge, Abigail SStančáková, AlenaAbrol, RavinderBesse, CélineBoland, AnneBork-Jensen, JetteFornage, MyriamFreitag, Daniel FGarcia, Melissa EGuo, XiuqingHara, KazuoIsaacs, AaronJakobsdottir, JohannaLange, Leslie ALayton, Jill CLi, ManHua Zhao, JingMeidtner, KarinaMorrison, Alanna CNalls, Mike APeters, Marjolein JSabater-Lleal, MariaSchurmann, ClaudiaSilveira, AngelaSmith, Albert VSoutham, LorraineStoiber, Marcus HStrawbridge, Rona JTaylor, Kent DVarga, Tibor VAllin, Kristine HAmin, NajafAponte, Jennifer LAung, TinBarbieri, CaterinaBihlmeyer, Nathan ABoehnke, MichaelBombieri, CristinaBowden, Donald WBurns, SeanChen, YuningChen, Yii-DerICheng, Ching-YuCorrea, AdolfoCzajkowski, JacekDehghan, AbbasEhret, Georg BEiriksdottir, GudnyEscher, Stefan AFarmaki, Aliki-EleniFrånberg, MattiasGambaro, GiovanniGiulianini, FrancoGoddard, William AGoel, AnujGottesman, OmriGrove, Megan LGustafsson, StefanHai, YangHallmans, GöranHeo, JiyoungHoffmann, PerIkram, Mohammad KJensen, Richard AJørgensen, Marit EJørgensen, TorbenKaraleftheri, MariaKhor, Chiea CKirkpatrick, AndreaKraja, Aldi TKuusisto, JohannaLange, Ethan MLee, I TLee, Wen-JaneLeong, AaronLiao, JieminLiu, ChunyuLiu, YongmeiLindgren, Cecilia MLinneberg, AllanMalerba, GiovanniMamakou, VasilikiMarouli, EiriniMaruthur, Nisa MMatchan, AngelaMcKean-Cowdin, RobertaMcLeod, OlgaMetcalf, Ginger AMohlke, Karen LMuzny, Donna MNtalla, IoannaPalmer, Nicholette DPasko, DorotaPeter, AndreasRayner, Nigel WRenström, FridaRice, KenSala, Cinzia FSennblad, BengtSerafetinidis, IoannisSmith, Jennifer ASoranzo, NicoleSpeliotes, Elizabeth KStahl, Eli AStirrups, KathleenTentolouris, NikosThanopoulou, AnastasiaTorres, MinaTraglia, MichelaTsafantakis, EmmanouilJavad, SundasYanek, Lisa RZengini, EleniBecker, Diane MBis, Joshua CBrown, James BAdrienne Cupples, LHansen, TorbenIngelsson, ErikKarter, Andrew JLorenzo, CarlosMathias, Rasika ANorris, Jill MPeloso, Gina MSheu, Wayne H.-H.Toniolo, DanielaVaidya, DhananjayVarma, RohitWagenknecht, Lynne EBoeing, HeinerBottinger, Erwin PDedoussis, GeorgeDeloukas, PanosFerrannini, EleFranco, Oscar HFranks, Paul WGibbs, Richard AGudnason, VilmundurHamsten, AndersHarris, Tamara BHattersley, Andrew THayward, CarolineHofman, AlbertJansson, Jan-HåkanLangenberg, ClaudiaLauner, Lenore JLevy, DanielOostra, Ben AO'Donnell, ChristopherO'Rahilly, StephenPadmanabhan, SandoshPankow, James SPolasek, OzrenProvince, Michael ARich, Stephen SRidker, PaulRudan, IgorSchulze, Matthias BSmith, Blair HUitterlinden, André GWalker, MarkWatkins, HughWong, Tien YZeggini, EleftheriaSharp, Stephen JForouhi, Nita GKerrison, Nicola DLucarelli, Debora MESims, MattBarroso, InêsMcCarthy, Mark IArriola, LarraitzBalkau, BeverleyBarricarte, AurelioGonzalez, CarlosGrioni, SaraKaaks, RudolfKey, Timothy JNavarro, CarmenNilsson, Peter MOvervad, KimPalli, DomenicoPanico, SalvatoreQuirós, J. RamónRolandsson, OlovSacerdote, CarlottaSánchez, María–JoséSlimani, NadiaTjonneland, AnneTumino, Rosariovan der A, Daphne Lvan der Schouw, Yvonne TRiboli, ElioLaakso, MarkkuBorecki, Ingrid BChasman, DanielPedersen, OlufPsaty, Bruce MShyong Tai, Evan Duijn, Cornelia MWareham, Nicholas JWaterworth, Dawn MBoerwinkle, EricLinda Kao, W HFlorez, JoseLoos, Ruth J.F.Wilson, James GFrayling, Timothy MSiscovick, David SDupuis, JoséeRotter, Jerome IMeigs, JamesScott, Robert AGoodarzi, Mark O2015-04-012015Wessel, J., A. Y. Chu, S. M. Willems, S. Wang, H. Yaghootkar, J. A. Brody, M. Dauriz, et al. 2015. “Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.” Nature Communications 6 (1): 5897. doi:10.1038/ncomms6897. http://dx.doi.org/10.1038/ncomms6897.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351066Fasting 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-USJournal Article2015-04-0110.1038/ncomms6897