期刊
NATURE GENETICS
卷 41, 期 1, 页码 77-81出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.290
关键词
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资金
- MRC [MC_U106188470, G0601261, G0701863] Funding Source: UKRI
- Intramural NIH HHS [Z01 HG000024] Funding Source: Medline
- Medical Research Council [G0500539, G0601261, G016121, G0000649, MC_U106179471, G0701863, MC_U106188470] Funding Source: Medline
- NCRR NIH HHS [RR-163736] Funding Source: Medline
- NHGRI NIH HHS [HG-02651, R01 HG002651, R01 HG002651-05] Funding Source: Medline
- NHLBI NIH HHS [HC-25195, R01 HL087679-02, HL-087679, U01 HL084729-03, HL-084729, R01 HL087679, U01 HL084729, N01 HC025195, N01HC25195, N02-HL-6-4278] Funding Source: Medline
- NIDA NIH HHS [U54 DA021519-04, U54 DA021519, DA-021519] Funding Source: Medline
- NIDDK NIH HHS [R01 DK078616-01A1, R01 DK069922-02, K24 DK080140-02, DK-080140, R01 DK072193, K23 DK065978-05, R01 DK072193-04, R01 DK062370, R01 DK078616, K24 DK080140, U01 DK078616, DK-072193, R01 DK069922, K24 DK080140-01, K23 DK065978, U01 DK062370, DK-065978, DK069922, R56 DK062370, R01 DK029867, DK-062370, DK-078616, R01 DK062370-05] Funding Source: Medline
- NIMH NIH HHS [R01 MH059160-04, MH059160] Funding Source: Medline
- Wellcome Trust [090532, 079557, 077011, 083948, 076113, GR072960, GR069224, 089061, 077016] Funding Source: Medline
- DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS [N01HC025195] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006094, U01HL084729, R01HL087679, R01HL064278] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG002651, ZIAHG000024, Z01HG000024] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK062370, K24DK080140, R01DK029867, R56DK062370, K23DK065978, U01DK078616, U01DK062370, R01DK069922, R01DK072193, R01DK078616] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH059160] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [ZIAAG000675] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [U54DA021519] Funding Source: NIH RePORTER
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.
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