Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.
In: Nature communications, Jg. 6 (2015-01-29), S. 5897
Online
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Zugriff:
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.
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.
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| Autor/in / Beteiligte Person: | Wessel, J ; Chu, AY ; Willems, SM ; Wang, S ; Yaghootkar, H ; Brody, JA ; Dauriz, M ; 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, C ; 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 3rd ; 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, G ; 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 ; Cupples, LA ; 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 ; Tai, ES ; van Duijn CM ; Wareham, NJ ; Waterworth, DM ; Boerwinkle, E ; Kao, WH ; Florez, JC ; Loos, RJ ; Wilson, JG ; Frayling, TM ; Siscovick, DS ; Dupuis, J ; Rotter, JI ; Meigs, JB ; Scott, RA ; Goodarzi, MO |
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| Zeitschrift: | Nature communications, Jg. 6 (2015-01-29), S. 5897 |
| Veröffentlichung: | [London] : Nature Pub. Group, 2015 |
| Medientyp: | academicJournal |
| ISSN: | 2041-1723 (electronic) |
| DOI: | 10.1038/ncomms6897 |
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