期刊
PLOS GENETICS
卷 10, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1004517
关键词
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资金
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, HHSN268200782096C, S06GM008016-320107, S06GM008016-380111, 2M01RR010284, U01 NS041588, R01 DK084350, HHSC268200782096C]
- National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]
- NHLBI [N01-HC-65226, HL085251, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756, HL103612, HL120393, N02-HL-6-4278]
- National Institute on Aging (NIA) [AG023629]
- National Center for Advancing Translational Sciences, CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]
- National Center of Advancing Translational Technologies CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- NHGRI
- NIGMS [U01-HG-004610, U01-HG-004608, U01-HG-04599, U01HG004609, U01-HG-04603]
- State of Washington Life Sciences Discovery Fund
- National Center for Research Resources [UL1RR025741]
- Vanderbilt CTSA from NCATS/NIH [UL1 TR000445]
- NIH from NHLBI [R01-HL-087700, R01-HL-088215]
- NIH from NIDDK [R01-DK-8925601, R01-DK-075681]
- FIND [U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, U01DK57304]
- NIH National Cancer Institute (NCI) [N01-CO-12400]
- NIH-NCI Center for Cancer Research
- National Center for Research Resources for the General Clinical Research Center [M01-RR-000080]
- Wake Forest University [M01-RR-07122]
- Harbor-University of California, Los Angeles Medical Center [M01-RR-00425]
- College of Medicine, University of California, Irvine [M01-RR-00827-29]
- University of New Mexico [HSC M01-RR-00997]
- Agency for Healthcare Research and Quality, Rockville, MD [HS08365]
- National Heart, Lung, and Blood Institute, Bethesda, MD [HL62985]
- NIH through the National Heart, Lung, and Blood Institute [HL58625-01A1, HL59684, HL071025-01A1, U01HL72518, HL087698]
- National Institute of Nursing Research [NR0224103]
- National Institutes of Health from the National Heart, Lung, and Blood Institute [HL087660, HL100245, HL100185]
- NIH, National Institute on Aging
- National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]
- NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- Center for Research on Genomics and Global Health (CRGGH)
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Center for Information Technology
- Office of the Director at the National Institutes of Health [Z01HG200362]
- Andrea and Charles Bronfman Philanthropies
- National Institute on Minority Health and Health Disparities
- National Heart, Lung, and Blood Institute (NHLBI)
- US EPA -Science to Achieve Results (STAR) Program [RD831697]
- National Center for Advancing Translational Sciences Grant [UL1TR000124]
- Vanderbilt-Ingram Cancer Center [P30 CA68485]
- U.S. NIH [R01CA92447]
- NIH [K99 DK081350, R01 DK066358, R01 DK053591, R01 HL56266, R01 DK070941]
- General Clinical Research Center of the Wake Forest School of Medicine [M01 RR07122]
- National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [N01-WH-22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]
- NHLBI Contract [N02-HL-64278]
- Burroughs Wellcome Fund Inter-school Training Program in Metabolic Diseases
- UCLA Genomic Analysis Training Program (NHGRI) [T32-HG002536]
- National Heart, Lung and Blood Institute [HL047887, HL047889, HL047890, HL47902, HL060944, HL060894, HL061210, HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]
- [R01HL087641]
- [R01HL59367]
- [R01HL086694]
- [N01-HC-48047]
- [N01-HC-48048]
- [N01-HC-48049]
- [N01-HC-48050]
- [N01-HC-95095]
- [N01-HC-45204]
- [N01-HC-45205]
- [N01-HC-05187]
- [N01-HC-45134]
- [N01-HC-95100]
- [NIH HL 46380]
- [M01RR00080]
- [M01-RR-01346]
- [M01-RR000052]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-RR-024156]
- Medical Research Council [MC_UU_12015/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10219] Funding Source: researchfish
- MRC [MC_PC_U127592696, MC_UU_12015/1] Funding Source: UKRI
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15x10(-94) < P < 5x10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2x10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.
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