Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
Article Details
- CitationCopy to clipboard
Reich D, Patterson N, Ramesh V, De Jager PL, McDonald GJ, Tandon A, Choy E, Hu D, Tamraz B, Pawlikowska L, Wassel-Fyr C, Huntsman S, Waliszewska A, Rossin E, Li R, Garcia M, Reiner A, Ferrell R, Cummings S, Kwok PY, Harris T, Zmuda JM, Ziv E
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
Am J Hum Genet. 2007 Apr;80(4):716-26. Epub 2007 Mar 8.
- PubMed ID
- 17357077 [ View in PubMed]
- Abstract
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<<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<<1.0x10-12 for IL-6 SR, and P<2.0x10-9 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.