title: Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, New Research Building, Boston, MA 02115, USA. reich@genetics.med.harvard.edu
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Vijaya
authors.initials: V
authors.lastname: Ramesh
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: McDonald
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.forename: Bani
authors.initials: B
authors.lastname: Tamraz
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Christina
authors.initials: C
authors.lastname: Wassel-Fyr
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.forename: Alicja
authors.initials: A
authors.lastname: Waliszewska
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rossin
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.forename: Alexander
authors.initials: A
authors.lastname: Reiner
authors.forename: Robert
authors.initials: R
authors.lastname: Ferrell
authors.forename: Steve
authors.initials: S
authors.lastname: Cummings
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Tamara
authors.initials: T
authors.lastname: Harris
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008126:Lod Score; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012984:Software; D044465:White People / Q000235:genetics
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6