Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
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.
Reich
David
D
Department of Genetics, Harvard Medical School, New Research Building, Boston, MA 02115, USA. reich@genetics.med.harvard.edu
Patterson
Nick
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Ramesh
Vijaya
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De Jager
Philip L
PL
McDonald
Gavin J
GJ
Tandon
Arti
A
Choy
Edwin
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Hu
Donglei
D
Tamraz
Bani
B
Pawlikowska
Ludmila
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Wassel-Fyr
Christina
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Huntsman
Scott
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Waliszewska
Alicja
A
Rossin
Elizabeth
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Li
Rongling
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Garcia
Melissa
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Reiner
Alexander
A
Ferrell
Robert
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Cummings
Steve
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Kwok
Pui-Yan
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Harris
Tamara
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Zmuda
Joseph M
JM
Ziv
Elad
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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
D015850:Interleukin-6; D019947:Receptors, Interleukin-6