Variants in MTNR1B influence fasting glucose levels

I Prokopenko; C Langenberg; JC Florez; R Saxena; N Soranzo; G Thorleifsson; RJF Loos; AK Manning; AU Jackson; Yuriy Aulchenko; SC Potter; MR Erdos; S Sanna; JJ (Jouke Jan) Hottenga; E Wheeler; M Kaakinen; V Lyssenko; WM Chen; K Ahmadi; JS Beckmann; RN Bergman; M Bochud; LL Bonnycastle; TA Buchanan; A Cao; A Cervino; L Coin; FS Collins; L Crisponi; EJC de Geus; Abbas Dehghan; P Deloukas; ASF Doney; P Elliott; N Freimer; V Gateva; Cindy Herder; Bert Hofman; TE Hughes; S Hunt; T Illig; M Inouye; B Isomaa; T Johnson; A Kong; M Krestyaninova; J Kuusisto; M Laakso; N Lim; U Lindblad; CM Lindgren; OT McCann; KL Mohlke; AD Morris; S Naitza; M Orru; CNA Palmer; A Pouta; J Randall; W Rathmann; J Saramies; P Scheet; LJ Scott; A Scuteri; S Sharp; E.J.G. Sijbrands; JH Smit; K Song; V Steinthorsdottir; HM Stringham; T Tuomi; J Tuomilehto; André Uitterlinden; BF Voight; D Waterworth; HE Wichmann; G Willemsen; JCM Witteman; X Yuan; JH Zhao; E Zeggini; D Schlessinger; M Sandhu; DI Boomsma; M Uda; TD Spector; BWJH Penninx; D Altshuler; P Vollenweider; MR Jarvelin; E Lakatta; G Waeber; CS Fox; L Peltonen; LC Groop; V Mooser; LA Cupples; U Thorsteinsdottir; M Boehnke

doi:10.1038/ng.290

Variants in MTNR1B influence fasting glucose levels

I Prokopenko, C Langenberg, JC Florez, R Saxena, N Soranzo, G Thorleifsson, RJF Loos, AK Manning, AU Jackson, Yuriy Aulchenko, SC Potter, MR Erdos, S Sanna, JJ (Jouke Jan) Hottenga, E Wheeler, M Kaakinen, V Lyssenko, WM Chen, K Ahmadi, JS BeckmannRN Bergman, M Bochud, LL Bonnycastle, TA Buchanan, A Cao, A Cervino, L Coin, FS Collins, L Crisponi, EJC de Geus, Abbas Dehghan, P Deloukas, ASF Doney, P Elliott, N Freimer, V Gateva, Cindy Herder, Bert Hofman, TE Hughes, S Hunt, T Illig, M Inouye, B Isomaa, T Johnson, A Kong, M Krestyaninova, J Kuusisto, M Laakso, N Lim, U Lindblad, CM Lindgren, OT McCann, KL Mohlke, AD Morris, S Naitza, M Orru, CNA Palmer, A Pouta, J Randall, W Rathmann, J Saramies, P Scheet, LJ Scott, A Scuteri, S Sharp, E.J.G. Sijbrands, JH Smit, K Song, V Steinthorsdottir, HM Stringham, T Tuomi, J Tuomilehto, André Uitterlinden, BF Voight, D Waterworth, HE Wichmann, G Willemsen, JCM Witteman, X Yuan, JH Zhao, E Zeggini, D Schlessinger, M Sandhu, DI Boomsma, M Uda, TD Spector, BWJH Penninx, D Altshuler, P Vollenweider, MR Jarvelin, E Lakatta, G Waeber, CS Fox, L Peltonen, LC Groop, V Mooser, LA Cupples, U Thorsteinsdottir, M Boehnke

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Original language	Undefined/Unknown
Pages (from-to)	77-81
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.290
Publication status	Published - 2009

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Access to Document

10.1038/ng.290

http://hdl.handle.net/1765/25072

Cite this

Prokopenko, I., Langenberg, C., Florez, JC., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, RJF., Manning, AK., Jackson, AU., Aulchenko, Y., Potter, SC., Erdos, MR., Sanna, S., Hottenga, JJ., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, WM., Ahmadi, K., ... Boehnke, M. (2009). Variants in MTNR1B influence fasting glucose levels. Nature Genetics, 41(1), 77-81. https://doi.org/10.1038/ng.290

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title = "Variants in MTNR1B influence fasting glucose levels",

abstract = "To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.",

author = "I Prokopenko and C Langenberg and JC Florez and R Saxena and N Soranzo and G Thorleifsson and RJF Loos and AK Manning and AU Jackson and Yuriy Aulchenko and SC Potter and MR Erdos and S Sanna and Hottenga, {JJ (Jouke Jan)} and E Wheeler and M Kaakinen and V Lyssenko and WM Chen and K Ahmadi and JS Beckmann and RN Bergman and M Bochud and LL Bonnycastle and TA Buchanan and A Cao and A Cervino and L Coin and FS Collins and L Crisponi and {de Geus}, EJC and Abbas Dehghan and P Deloukas and ASF Doney and P Elliott and N Freimer and V Gateva and Cindy Herder and Bert Hofman and TE Hughes and S Hunt and T Illig and M Inouye and B Isomaa and T Johnson and A Kong and M Krestyaninova and J Kuusisto and M Laakso and N Lim and U Lindblad and CM Lindgren and OT McCann and KL Mohlke and AD Morris and S Naitza and M Orru and CNA Palmer and A Pouta and J Randall and W Rathmann and J Saramies and P Scheet and LJ Scott and A Scuteri and S Sharp and E.J.G. Sijbrands and JH Smit and K Song and V Steinthorsdottir and HM Stringham and T Tuomi and J Tuomilehto and Andr{\'e} Uitterlinden and BF Voight and D Waterworth and HE Wichmann and G Willemsen and JCM Witteman and X Yuan and JH Zhao and E Zeggini and D Schlessinger and M Sandhu and DI Boomsma and M Uda and TD Spector and BWJH Penninx and D Altshuler and P Vollenweider and MR Jarvelin and E Lakatta and G Waeber and CS Fox and L Peltonen and LC Groop and V Mooser and LA Cupples and U Thorsteinsdottir and M Boehnke",

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doi = "10.1038/ng.290",

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Prokopenko, I, Langenberg, C, Florez, JC, Saxena, R, Soranzo, N, Thorleifsson, G, Loos, RJF, Manning, AK, Jackson, AU, Aulchenko, Y, Potter, SC, Erdos, MR, Sanna, S, Hottenga, JJ, Wheeler, E, Kaakinen, M, Lyssenko, V, Chen, WM, Ahmadi, K, Beckmann, JS, Bergman, RN, Bochud, M, Bonnycastle, LL, Buchanan, TA, Cao, A, Cervino, A, Coin, L, Collins, FS, Crisponi, L, de Geus, EJC, Dehghan, A, Deloukas, P, Doney, ASF, Elliott, P, Freimer, N, Gateva, V, Herder, C, Hofman, B, Hughes, TE, Hunt, S, Illig, T, Inouye, M, Isomaa, B, Johnson, T, Kong, A, Krestyaninova, M, Kuusisto, J, Laakso, M, Lim, N, Lindblad, U, Lindgren, CM, McCann, OT, Mohlke, KL, Morris, AD, Naitza, S, Orru, M, Palmer, CNA, Pouta, A, Randall, J, Rathmann, W, Saramies, J, Scheet, P, Scott, LJ, Scuteri, A, Sharp, S, Sijbrands, EJG, Smit, JH, Song, K, Steinthorsdottir, V, Stringham, HM, Tuomi, T, Tuomilehto, J, Uitterlinden, A, Voight, BF, Waterworth, D, Wichmann, HE, Willemsen, G, Witteman, JCM, Yuan, X, Zhao, JH, Zeggini, E, Schlessinger, D, Sandhu, M, Boomsma, DI, Uda, M, Spector, TD, Penninx, BWJH, Altshuler, D, Vollenweider, P, Jarvelin, MR, Lakatta, E, Waeber, G, Fox, CS, Peltonen, L, Groop, LC, Mooser, V, Cupples, LA, Thorsteinsdottir, U & Boehnke, M 2009, 'Variants in MTNR1B influence fasting glucose levels', Nature Genetics, vol. 41, no. 1, pp. 77-81. https://doi.org/10.1038/ng.290

TY - JOUR

T1 - Variants in MTNR1B influence fasting glucose levels

AU - Prokopenko, I

AU - Langenberg, C

AU - Florez, JC

AU - Saxena, R

AU - Soranzo, N

AU - Thorleifsson, G

AU - Loos, RJF

AU - Manning, AK

AU - Jackson, AU

AU - Aulchenko, Yuriy

AU - Potter, SC

AU - Erdos, MR

AU - Sanna, S

AU - Hottenga, JJ (Jouke Jan)

AU - Wheeler, E

AU - Kaakinen, M

AU - Lyssenko, V

AU - Chen, WM

AU - Ahmadi, K

AU - Beckmann, JS

AU - Bergman, RN

AU - Bochud, M

AU - Bonnycastle, LL

AU - Buchanan, TA

AU - Cao, A

AU - Cervino, A

AU - Coin, L

AU - Collins, FS

AU - Crisponi, L

AU - de Geus, EJC

AU - Dehghan, Abbas

AU - Deloukas, P

AU - Doney, ASF

AU - Elliott, P

AU - Freimer, N

AU - Gateva, V

AU - Herder, Cindy

AU - Hofman, Bert

AU - Hughes, TE

AU - Hunt, S

AU - Illig, T

AU - Inouye, M

AU - Isomaa, B

AU - Johnson, T

AU - Kong, A

AU - Krestyaninova, M

AU - Kuusisto, J

AU - Laakso, M

AU - Lim, N

AU - Lindblad, U

AU - Lindgren, CM

AU - McCann, OT

AU - Mohlke, KL

AU - Morris, AD

AU - Naitza, S

AU - Orru, M

AU - Palmer, CNA

AU - Pouta, A

AU - Randall, J

AU - Rathmann, W

AU - Saramies, J

AU - Scheet, P

AU - Scott, LJ

AU - Scuteri, A

AU - Sharp, S

AU - Sijbrands, E.J.G.

AU - Smit, JH

AU - Song, K

AU - Steinthorsdottir, V

AU - Stringham, HM

AU - Tuomi, T

AU - Tuomilehto, J

AU - Uitterlinden, André

AU - Voight, BF

AU - Waterworth, D

AU - Wichmann, HE

AU - Willemsen, G

AU - Witteman, JCM

AU - Yuan, X

AU - Zhao, JH

AU - Zeggini, E

AU - Schlessinger, D

AU - Sandhu, M

AU - Boomsma, DI

AU - Uda, M

AU - Spector, TD

AU - Penninx, BWJH

AU - Altshuler, D

AU - Vollenweider, P

AU - Jarvelin, MR

AU - Lakatta, E

AU - Waeber, G

AU - Fox, CS

AU - Peltonen, L

AU - Groop, LC

AU - Mooser, V

AU - Cupples, LA

AU - Thorsteinsdottir, U

AU - Boehnke, M

PY - 2009

Y1 - 2009

N2 - To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

AB - To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

U2 - 10.1038/ng.290

DO - 10.1038/ng.290

M3 - Article

C2 - 19060907

SN - 1061-4036

VL - 41

SP - 77

EP - 81

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -