Variants in MTNR1B influence fasting glucose levels.

Prokopenko, I.; Langenberg, C.; Florez, J.C.; Saxena, R.; Soranzo, N.; Thorleifsson, G.; Loos, R.J.; Manning, A.K.; Jackson, A.U.; Aulchenko, Y.; Potter, S.C.; Erdos, M.R.; Sanna, S.; Hottenga, J.J.; Wheeler, E.; Kaakinen, M.; Lyssenko, V.; Chen, W.M.; Ahmadi, K.; Beckmann, J.S.; Bergman, R.N.; Bochud, M.; Bonnycastle, L.L.; Buchanan, T.A.; Cao, A.; Cervino, A.; Coin, L.; Collins, F.S.; Crisponi, L.; de Geus, E.J.; Dehghan, A.; Deloukas, P.; Doney, A.S.; Elliott, P.; Freimer, N.; Gateva, V.; Herder, C.; Hofman, A.; Hughes, T.E.; Hunt, S.; Illig, T.; Inouye, M.; Isomaa, B.; Johnson, T.; Kong, A.; Krestyaninova, M.; Kuusisto, J.; Laakso, M.; Lim, N.; Lindblad, U.; Lindgren, C.M.; McCann, O.T.; Mohlke, K.L.; Morris, A.D.; Naitza, S.; Orrù, M.; Palmer, C.N.; Pouta, A.; Randall, J.; Rathmann, W.; Saramies, J.; Scheet, P.; Scott, L.J.; Scuteri, A.; Sharp, S.; Sijbrands, E.; Smit, J.H.; Song, K.; Steinthorsdottir, V.; Stringham, H.M.; Tuomi, T.; Tuomilehto, J.; Uitterlinden, A.G.; Voight, B.F.; Waterworth, D.; Wichmann, H.E.; Willemsen, G.; Witteman, J.C.; Yuan, X.; Zhao, J.H.; Zeggini, E.; Schlessinger, D.; Sandhu, M.; Boomsma, D.I.; Uda, M.; Spector, T.D.; Penninx, B.W.; Altshuler, D.; Vollenweider, P.; Jarvelin, M.R.; Lakatta, E.; Waeber, G.; Fox, C.S.; Peltonen, L.; Groop, L.C.; Mooser, V.; Cupples, L.A.; Thorsteinsdottir, U.; Boehnke, M.; Barroso, I.; Van Duijn, C.; Dupuis, J.; Watanabe, R.M.; Stefansson, K.; McCarthy, M.I.; Wareham, N.J.; Meigs, J.B.; Abecasis, G.R.

doi:10.1038/ng.290

Variants in MTNR1B influence fasting glucose levels.

Détails

Télécharger: 5_19060907_Postprint.pdf (1644.17 [Ko])
Etat: Public
Version: Author's accepted manuscript

ID Serval

serval:BIB_2AFD50467B1C

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

Variants in MTNR1B influence fasting glucose levels.

Périodique

Nature Genetics

Auteur⸱e⸱s

Prokopenko I., Langenberg C., Florez J.C., Saxena R., Soranzo N., Thorleifsson G., Loos R.J., Manning A.K., Jackson A.U., Aulchenko Y., Potter S.C., Erdos M.R., Sanna S., Hottenga J.J., Wheeler E., Kaakinen M., Lyssenko V., Chen W.M., Ahmadi K., Beckmann J.S., Bergman R.N., Bochud M., Bonnycastle L.L., Buchanan T.A., Cao A., Cervino A., Coin L., Collins F.S., Crisponi L., de Geus E.J., Dehghan A., Deloukas P., Doney A.S., Elliott P., Freimer N., Gateva V., Herder C., Hofman A., Hughes T.E., Hunt S., Illig T., Inouye M., Isomaa B., Johnson T., Kong A., Krestyaninova M., Kuusisto J., Laakso M., Lim N., Lindblad U., Lindgren C.M., McCann O.T., Mohlke K.L., Morris A.D., Naitza S., Orrù M., Palmer C.N., Pouta A., Randall J., Rathmann W., Saramies J., Scheet P., Scott L.J., Scuteri A., Sharp S., Sijbrands E., Smit J.H., Song K., Steinthorsdottir V., Stringham H.M., Tuomi T., Tuomilehto J., Uitterlinden A.G., Voight B.F., Waterworth D., Wichmann H.E., Willemsen G., Witteman J.C., Yuan X., Zhao J.H., Zeggini E., Schlessinger D., Sandhu M., Boomsma D.I., Uda M., Spector T.D., Penninx B.W., Altshuler D., Vollenweider P., Jarvelin M.R., Lakatta E., Waeber G., Fox C.S., Peltonen L., Groop L.C., Mooser V., Cupples L.A., Thorsteinsdottir U., Boehnke M., Barroso I., Van Duijn C., Dupuis J., Watanabe R.M., Stefansson K., McCarthy M.I., Wareham N.J., Meigs J.B., Abecasis G.R.

ISSN

1546-1718

Statut éditorial

Publié

Date de publication

2009

Peer-reviewed

Oui

Volume

Numéro

Pages

77-81

Langue

anglais

Résumé

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.

Mots-clé

Blood Glucose, Case-Control Studies, Diabetes Mellitus, Type 2, Fasting, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptor, Melatonin, MT2, Receptors, Melatonin, Colaus Study

URN

urn:nbn:ch:serval-BIB_2AFD50467B1C9

OAI-PMH

oai:serval.unil.ch:BIB_2AFD50467B1C

DOI

10.1038/ng.290

Pubmed

19060907

Web of science

000262085300019

Création de la notice

20/02/2009 14:21