期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 80, 期 4, 页码 716-726出版社
CELL PRESS
DOI: 10.1086/513206
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资金
- NCI NIH HHS [K22 CA109351] Funding Source: Medline
- NCRR NIH HHS [U54 RR020278] Funding Source: Medline
- NIA NIH HHS [N01 AG062101, N01 AG062103, N01 AG062106, R01 AG021024] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007753] Funding Source: Medline
- NINDS NIH HHS [P30 NS045776] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [K22CA109351] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020278] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007753] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P30NS045776] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [N01AG062101, Z01AG007390, N01AG062103, R01AG021024, N01AG062106] Funding Source: NIH RePORTER
Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P << 1.0 x 10(-12)) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P < 3.4 x 10(-5)). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P << 1.0 x 10(-12) for IL-6 SR, and P < 2.0 x 10(-9) for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant.
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