期刊
NATURE GENETICS
卷 42, 期 2, 页码 142-U75出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.521
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资金
- British Heart Foundation [RG/07/008/23674] Funding Source: Medline
- Intramural NIH HHS [Z01 HG000024-14] Funding Source: Medline
- Medical Research Council [MC_U106179471, MC_U106188470, G19/35, G8802774, G0600331, MC_UP_A620_1014, MC_UP_A620_1015, G0701863, G0100222, G0902037] Funding Source: Medline
- NCI NIH HHS [P01 CA087969-12, P01 CA087969] Funding Source: Medline
- NCRR NIH HHS [M01 RR001066, M01 RR001066-26, M01 RR000052, M01 RR016500, M01 RR016500-08, M01 RR000052-46] Funding Source: Medline
- NHGRI NIH HHS [U01 HG004402-02, U01 HG004399-02, U01 HG004399, U01 HG004402] Funding Source: Medline
- NHLBI NIH HHS [R01 HL086694, N02 HL64278, R01 HL036310, R01 HL036310-21, N01 HC055222, R01 HL087641, N01 HC085079, N01 HC085086, N01 HC055022, U01 HL072515-06, U01 HL072515, R01 HL059367, N01 HC055021, N01 HC085085, N01 HC075150, R01 HL059367-10, R01 HL087652, U01 HL080295, N01 HC085080, R01 HL087652-03, N01 HC035129, N01 HC015103, R01 HL086694-03, N01 HC085083, N01 HC055015, N01 HC055018, U01 HL080295-04, N01 HC085081, N01 HC045133, N01 HC055016, N01 HC085084, N01 HC055020, R01 HL087641-03, N01 HC055019, N01 HC085082, N01 HC025195] Funding Source: Medline
- NIA NIH HHS [R01 AG013196, R01 AG013196-16] Funding Source: Medline
- NIDA NIH HHS [U54 DA021519-04, U54 DA021519] Funding Source: Medline
- NIDDK NIH HHS [R01 DK069922, P30 DK072488, R01 DK054261-09, K23 DK065978-05, P60 DK079637, R01 DK078616, R01 DK029867, R01 DK072193, R01 DK072193-04, P30 DK072488-06, R01 DK054261, K23 DK065978, K24 DK080140-04, R01 DK078616-03, R01 DK062370-05, R01 DK058845-11, R01 DK069922-03, P30 DK079637, P60 DK079637-04, K24 DK080140, R01 DK058845, R01 DK091718, R01 DK062370] Funding Source: Medline
- Wellcome Trust [088885, 077016] Funding Source: Medline
- Chief Scientist Office [CZB/4/710] Funding Source: Medline
- MRC [MC_UP_A620_1015, G0600331, G0701863, MC_U106188470, G0902037] 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_UP_A620_1014, G0701863, G0600331, U1475000001, G0902037, MC_UP_A620_1015, G0600717B, G0100222, U1475000002, G19/35, G8802774, MC_U106179471, MC_U106188470] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10082] Funding Source: researchfish
Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).
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