Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels

Am J Hum Genet. 2007 Apr;80(4):716-26. doi: 10.1086/513206. Epub 2007 Mar 8.


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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Black or African American / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics*
  • Female
  • Gene Frequency
  • Genomics / methods
  • Genotype
  • Humans
  • Interleukin-6 / blood*
  • Lod Score
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Interleukin-6 / genetics*
  • Software*
  • White People / genetics


  • Interleukin-6
  • Receptors, Interleukin-6