Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.
| Title: | Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. |
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| Authors: | Wessel J; Chu AY; Willems SM; Wang S; Yaghootkar H; Brody JA; DAURIZ, Marco; Hivert MF; Raghavan S; Lipovich L; Hidalgo B; Fox K; Huffman JE; An P; Lu Y; Rasmussen Torvik LJ; Grarup N; Ehm MG; Li L; Baldridge AS; Stančáková A; Abrol R; Besse C; Boland A; Bork Jensen J; Fornage M; Freitag DF; Garcia ME; Guo X; Hara K; Isaacs A; Jakobsdottir J; Lange LA; Layton JC; Li M; Hua Zhao J; Meidtner K; Morrison AC; Nalls MA; Peters MJ; Sabater Lleal M; Schurmann C; Silveira A; Smith AV; Southam L; Stoiber MH; Strawbridge RJ; Taylor KD; Varga TV; Allin KH; Amin N; Aponte JL; Aung T; Barbieri C; Bihlmeyer NA; Boehnke M; BOMBIERI, Cristina; Bowden DW; Burns SM; Chen Y; Chen YD; Cheng CY; Correa A; Czajkowski J; Dehghan A; Ehret GB; Eiriksdottir G; Escher SA; Farmaki AE; Frånberg M; Gambaro G; Giulianini F; Goddard WA; Goel A; Gottesman O; Grove ML; Gustafsson S; Hai Y; Hallmans G; Heo J; Hoffmann P; Ikram MK; Jensen RA; Jørgensen ME; Jørgensen T; Karaleftheri M; Khor CC; Kirkpatrick A; Kraja AT; Kuusisto J; Lange EM; Lee IT; Lee WJ; Leong A; Liao J; Liu C; Liu Y; Lindgren CM; Linneberg A; MALERBA, Giovanni; Mamakou V; Marouli E; Maruthur NM; Matchan A; McKean Cowdin R; McLeod O; Metcalf GA; Mohlke KL; Muzny DM; Ntalla I; Palmer ND; Pasko D; Peter A; Rayner NW; Renström F; Rice K; Sala CF; Sennblad B; Serafetinidis I; Smith JA; Soranzo N; Speliotes EK; Stahl EA; Stirrups K; Tentolouris N; Thanopoulou A; Torres M; Traglia M; Tsafantakis E; Javad S; Yanek LR; Zengini E; Becker DM; Bis JC; Brown JB; Adrienne Cupples L; Hansen T; Ingelsson E; Karter AJ; Lorenzo C; Mathias RA; Norris JM; Peloso GM; Sheu WH; Toniolo D; Vaidya D; Varma R; Wagenknecht LE; Boeing H; Bottinger EP; Dedoussis G; Deloukas P; Ferrannini E; Franco OH; Franks PW; Gibbs RA; Gudnason V; Hamsten A; Harris TB; Hattersley AT; Hayward C; Hofman A; Jansson JH; Langenberg C; Launer LJ; Levy D; Oostra BA; O'Donnell CJ; O'Rahilly S; Padmanabhan S; Pankow JS; Polasek O; Province MA; Rich SS; Ridker PM; Rudan I; Schulze MB; Smith BH; Uitterlinden AG; Walker M; Watkins H; Wong TY; Zeggini E; Laakso M; Borecki IB; Chasman DI; Pedersen O; Psaty BM; Shyong Tai E; van Duijn CM; Wareham NJ; Waterworth DM; Boerwinkle E; Linda Kao WH; Florez JC; Loos RJ; Wilson JG; Frayling TM; Siscovick DS; Dupuis J; Rotter JI; Meigs JB; Scott RA; Goodarzi MO; EPIC InterAct Consortium |
| Contributors: | Wessel, J; Chu, Ay; Willems, Sm; Wang, S; Yaghootkar, H; Brody, Ja; Dauriz, Marco; Hivert, Mf; Raghavan, S; Lipovich, L; Hidalgo, B; Fox, K; Huffman, Je; An, P; Lu, Y; Rasmussen Torvik, Lj; Grarup, N; Ehm, Mg; Li, L; Baldridge, A; Stančáková, A; Abrol, R; Besse, C; Boland, A; Bork Jensen, J; Fornage, M; Freitag, Df; Garcia, Me; Guo, X; Hara, K; Isaacs, A; Jakobsdottir, J; Lange, La; Layton, Jc; Li, M; Hua Zhao, J; Meidtner, K; Morrison, Ac; Nalls, Ma; Peters, Mj; Sabater Lleal, M; Schurmann, C; Silveira, A; Smith, Av; Southam, L; Stoiber, Mh; Strawbridge, Rj; Taylor, Kd; Varga, Tv; Allin, Kh; Amin, N; Aponte, Jl; Aung, T; Barbieri, C; Bihlmeyer, Na; Boehnke, M; Bombieri, Cristina; Bowden, Dw; Burns, Sm; Chen, Y; Chen, Yd; Cheng, Cy; Correa, A; Czajkowski, J; Dehghan, A; Ehret, Gb; Eiriksdottir, G; Escher, Sa; Farmaki, Ae; Frånberg, M; Gambaro, G; Giulianini, F; Goddard, Wa; Goel, A; Gottesman, O; Grove, Ml; Gustafsson, S; Hai, Y; Hallmans, G; Heo, J; Hoffmann, P; Ikram, Mk; Jensen, Ra; Jørgensen, Me; Jørgensen, T; Karaleftheri, M; Khor, Cc; Kirkpatrick, A; Kraja, At; Kuusisto, J; Lange, Em; Lee, It; Lee, Wj; Leong, A; Liao, J; Liu, C; Liu, Y; Lindgren, Cm; Linneberg, A; Malerba, Giovanni |
| Publication Year: | 2015 |
| Collection: | Università degli Studi di Verona: Catalogo dei Prodotti della Ricerca (IRIS) |
| Subject Terms: | epidemiology/genetics; Cohort Studies; Exome; diabetes |
| Description: | Fasting 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. |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/25631608; info:eu-repo/semantics/altIdentifier/wos/WOS:000348741700001; volume:6; issue:5897; firstpage:1; lastpage:16; numberofpages:16; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/11562/881401; https://doi.org/10.1038/ncomms6897 |
| DOI: | 10.1038/ncomms6897 |
| Availability: | https://hdl.handle.net/11562/881401; https://doi.org/10.1038/ncomms6897 |
| Rights: | info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/3.0/it/ |
| Accession Number: | edsbas.892CE959 |
| Database: | BASE |