Details

Autor(en) / Beteiligte

• Reich, David
• Patterson, Nick
• Ramesh, Vijaya
• De Jager, Philip L.
• McDonald, Gavin J.
• Tandon, Arti
• Choy, Edwin
• Hu, Donglei
• Tamraz, Bani
• Pawlikowska, Ludmila
• Wassel-Fyr, Christina
• Huntsman, Scott
• Waliszewska, Alicja
• Rossin, Elizabeth
• Li, Rongling
• Garcia, Melissa
• Reiner, Alexander
• Ferrell, Robert
• Cummings, Steve
• Kwok, Pui-Yan
• Harris, Tamara
• Zmuda, Joseph M.
• Ziv, Elad

Titel

Admixture Mapping of an Allele Affecting Interleukin 6 Soluble Receptor and Interleukin 6 Levels

Ist Teil von

• American journal of human genetics, 2007-04, Vol.80 (4), p.716-726

Ort / Verlag

Chicago, IL: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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≪1.0×10 −12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 ( P<3.4×10 −5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P≪1.0×10 −12 for IL-6 SR, and P<2.0×10 −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.