期刊
NATURE GENETICS
卷 44, 期 6, 页码 659-U81出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2274
关键词
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资金
- British Heart Foundation [RG/07/008/23674] Funding Source: Medline
- Medical Research Council [MC_U137686857, MC_U127561128, G0100222, G19/35, MC_U106179472, MC_UP_A100_1003, MC_U106179471, MC_PC_U127561128, G1002084, G0902037, G0900339, G0701863, MC_PC_U127592696, MR/J006742/1, MC_U127592696, G8802774] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124] Funding Source: Medline
- NCRR NIH HHS [S10 RR029392] Funding Source: Medline
- NHLBI NIH HHS [R01 HL105756] Funding Source: Medline
- NIDDK NIH HHS [R01 DK093757, P30 DK020572, K24 DK080140, P30 DK063491, R01 DK078616, R01 DK072193] Funding Source: Medline
- NIMH NIH HHS [R37 MH059490] Funding Source: Medline
- Wellcome Trust [091551, 090532] Funding Source: Medline
- Chief Scientist Office [CZB/4/710] Funding Source: Medline
- MRC [MC_U127592696, MC_U106179472, MC_U127561128, G1002084, MC_U137686857, G0701863, G0902037, MC_PC_U127592696, G0900339, MC_UP_A100_1003, MC_PC_U127561128] Funding Source: UKRI
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [MC_U137686857, MC_U127592696, G0902037, G19/35, G0600717B, G0100222, G0900339, MC_PC_U127561128, MC_U106179472, MC_PC_U127592696, G8802774, G0701863, G0801056B, MR/J006742/1, MC_UP_A100_1003, MC_U106179471, MC_U127561128, G0600698B, G1002084] Funding Source: researchfish
- Novo Nordisk Fonden [NNF11OC1014855] Funding Source: researchfish
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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