Abstract
| Original language | English |
|---|---|
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| Publication status | Published - 2015 |
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. / 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, YC; Rasmussen-Torvik, LJ; Grarup, N; Ehm, MG; Li, Li; Baldridge, AS; Stancakova, A; Abrol, R; Besse, CL; Boland, A; Bork-Jensen, J; Fornage, M; Freitag, DF; Garcia, ME; Guo, XQ; Hara, K; Isaacs, Aaron; Jakobsdottir, J; Lange, LA; Layton, JC; Li, M; Zhao, JH; Meidtner, K; Morrison, AC; Nalls, MA; Peters, Marjolein; Sabater-Lleal, M; Schurmann, C; Silveira, A; Smith, AV; Southam, L; Stoiber, MH; Strawbridge, RJ; Taylor, KD; Varga, TV; Allin, KH; Amin, Najaf; Aponte, JL; Aung, T; Barbieri, C; Bihlmeyer, NA; Boehnke, M; Bombieri, C; Bowden, DW; Burns, SM; Chen, YN; Chen, YD; Cheng, CY (Ching-Yu); Correa, A; Czajkowski, J; Dehghan, Abbas; Ehret, GB; Eiriksdottir, G; Escher, SA; Farmaki, AE; Franberg, 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; Jorgensen, ME; Jorgensen, T; Karaleftheri, M; Khor, CC; Kirkpatrick, A; Kraja, AT; Kuusisto, J; Lange, Edmee; Lee, IT; Lee, WJ; Leong, A; Liao, JM; Liu, CY; Liu, YM; 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; Renstrom, 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, WHH; Toniolo, D; Vaidya, D; Varma, R; Wagenknecht, LE; Boeing, H; Bottinger, EP; Dedoussis, G; Deloukas, P; Ferrannini, E; Franco Duran, OH; Franks, PW; Gibbs, RA; Gudnason, V; Hamsten, A; Harris, TB; Hattersley, AT; Hayward, C; Hofman, Bert; Jansson, JH; Langenberg, C; Launer, LJ (Lenore); Levy, D; Oostra, Ben; 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, André; Walker, M; Watkins, H; Wong, TY (Tien Yin); Zeggini, E; Laakso, M; Borecki, IB; Chasman, DI; Pedersen, O; Psaty, BM; Tai, ES; Duijn, Cornelia; Wareham, NJ; Waterworth, DM; Boerwinkle, E; Kao, WHL; Florez, JC; Loos, RJF; Wilson, JG; Frayling, TM; Siscovick, DS; Dupuis, J; Rotter, JI; Meigs, JB; Scott, RA; Goodarzi, MO; Sharp, SJ; Forouhi, NG; Kerrison, ND; Lucarelli, DM; Sims, M; Barroso, I; McCarthy, MI; Arriola, L; Balkau, B; Barricarte, A; Gonzalez, C; Grioni, S; Kaaks, R; Key, TJ; Navarro, C; Nilsson, PM; Overvad, K; Palli, D; Panico, S; Quiros, JR; Rolandsson, O; Sacerdote, C; Sanchez, MJ (Maria-Jose); Slimani, N; Tjonneland, A; Tumino, R; van der A, DL; van der Schouw, YT; Riboli, E.
In: Nature Communications, Vol. 6, 2015.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
AU - Wessel, J
AU - Chu, AY
AU - Willems, SM
AU - Wang, S
AU - Yaghootkar, H
AU - Brody, JA
AU - Dauriz, M
AU - Hivert, MF
AU - Raghavan, S
AU - Lipovich, L
AU - Hidalgo, B
AU - Fox, K
AU - Huffman, JE
AU - An, P
AU - Lu, YC
AU - Rasmussen-Torvik, LJ
AU - Grarup, N
AU - Ehm, MG
AU - Li, Li
AU - Baldridge, AS
AU - Stancakova, A
AU - Abrol, R
AU - Besse, CL
AU - Boland, A
AU - Bork-Jensen, J
AU - Fornage, M
AU - Freitag, DF
AU - Garcia, ME
AU - Guo, XQ
AU - Hara, K
AU - Isaacs, Aaron
AU - Jakobsdottir, J
AU - Lange, LA
AU - Layton, JC
AU - Li, M
AU - Zhao, JH
AU - Meidtner, K
AU - Morrison, AC
AU - Nalls, MA
AU - Peters, Marjolein
AU - Sabater-Lleal, M
AU - Schurmann, C
AU - Silveira, A
AU - Smith, AV
AU - Southam, L
AU - Stoiber, MH
AU - Strawbridge, RJ
AU - Taylor, KD
AU - Varga, TV
AU - Allin, KH
AU - Amin, Najaf
AU - Aponte, JL
AU - Aung, T
AU - Barbieri, C
AU - Bihlmeyer, NA
AU - Boehnke, M
AU - Bombieri, C
AU - Bowden, DW
AU - Burns, SM
AU - Chen, YN
AU - Chen, YD
AU - Cheng, CY (Ching-Yu)
AU - Correa, A
AU - Czajkowski, J
AU - Dehghan, Abbas
AU - Ehret, GB
AU - Eiriksdottir, G
AU - Escher, SA
AU - Farmaki, AE
AU - Franberg, M
AU - Gambaro, G
AU - Giulianini, F
AU - Goddard, WA
AU - Goel, A
AU - Gottesman, O
AU - Grove, ML
AU - Gustafsson, S
AU - Hai, Y
AU - Hallmans, G
AU - Heo, J
AU - Hoffmann, P
AU - Ikram, MK
AU - Jensen, RA
AU - Jorgensen, ME
AU - Jorgensen, T
AU - Karaleftheri, M
AU - Khor, CC
AU - Kirkpatrick, A
AU - Kraja, AT
AU - Kuusisto, J
AU - Lange, Edmee
AU - Lee, IT
AU - Lee, WJ
AU - Leong, A
AU - Liao, JM
AU - Liu, CY
AU - Liu, YM
AU - Lindgren, CM
AU - Linneberg, A
AU - Malerba, G
AU - Mamakou, V
AU - Marouli, E
AU - Maruthur, NM
AU - Matchan, A
AU - McKean-Cowdin, R
AU - McLeod, O
AU - Metcalf, GA
AU - Mohlke, KL
AU - Muzny, DM
AU - Ntalla, I
AU - Palmer, ND
AU - Pasko, D
AU - Peter, A
AU - Rayner, NW
AU - Renstrom, F
AU - Rice, K
AU - Sala, CF
AU - Sennblad, B
AU - Serafetinidis, I
AU - Smith, JA
AU - Soranzo, N
AU - Speliotes, EK
AU - Stahl, EA
AU - Stirrups, K
AU - Tentolouris, N
AU - Thanopoulou, A
AU - Torres, M
AU - Traglia, M
AU - Tsafantakis, E
AU - Javad, S
AU - Yanek, LR
AU - Zengini, E
AU - Becker, DM
AU - Bis, JC
AU - Brown, JB
AU - Cupples, LA
AU - Hansen, T
AU - Ingelsson, E
AU - Karter, AJ
AU - Lorenzo, C
AU - Mathias, RA
AU - Norris, JM
AU - Peloso, GM
AU - Sheu, WHH
AU - Toniolo, D
AU - Vaidya, D
AU - Varma, R
AU - Wagenknecht, LE
AU - Boeing, H
AU - Bottinger, EP
AU - Dedoussis, G
AU - Deloukas, P
AU - Ferrannini, E
AU - Franco Duran, OH
AU - Franks, PW
AU - Gibbs, RA
AU - Gudnason, V
AU - Hamsten, A
AU - Harris, TB
AU - Hattersley, AT
AU - Hayward, C
AU - Hofman, Bert
AU - Jansson, JH
AU - Langenberg, C
AU - Launer, LJ (Lenore)
AU - Levy, D
AU - Oostra, Ben
AU - O'Donnell, CJ
AU - O'Rahilly, S
AU - Padmanabhan, S
AU - Pankow, JS
AU - Polasek, O
AU - Province, MA
AU - Rich, SS
AU - Ridker, PM
AU - Rudan, I
AU - Schulze, MB
AU - Smith, BH
AU - Uitterlinden, André
AU - Walker, M
AU - Watkins, H
AU - Wong, TY (Tien Yin)
AU - Zeggini, E
AU - Laakso, M
AU - Borecki, IB
AU - Chasman, DI
AU - Pedersen, O
AU - Psaty, BM
AU - Tai, ES
AU - Duijn, Cornelia
AU - Wareham, NJ
AU - Waterworth, DM
AU - Boerwinkle, E
AU - Kao, WHL
AU - Florez, JC
AU - Loos, RJF
AU - Wilson, JG
AU - Frayling, TM
AU - Siscovick, DS
AU - Dupuis, J
AU - Rotter, JI
AU - Meigs, JB
AU - Scott, RA
AU - Goodarzi, MO
AU - Sharp, SJ
AU - Forouhi, NG
AU - Kerrison, ND
AU - Lucarelli, DM
AU - Sims, M
AU - Barroso, I
AU - McCarthy, MI
AU - Arriola, L
AU - Balkau, B
AU - Barricarte, A
AU - Gonzalez, C
AU - Grioni, S
AU - Kaaks, R
AU - Key, TJ
AU - Navarro, C
AU - Nilsson, PM
AU - Overvad, K
AU - Palli, D
AU - Panico, S
AU - Quiros, JR
AU - Rolandsson, O
AU - Sacerdote, C
AU - Sanchez, MJ (Maria-Jose)
AU - Slimani, N
AU - Tjonneland, A
AU - Tumino, R
AU - van der A, DL
AU - van der Schouw, YT
AU - Riboli, E
PY - 2015
Y1 - 2015
N2 - 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 (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 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 (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
AB - 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 (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 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 (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
U2 - 10.1038/ncomms6897
DO - 10.1038/ncomms6897
M3 - Article
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -