title: A genome-wide admixture scan for ancestry-linked genes predisposing to sarcoidosis in African-Americans.
abstract: Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multiorgan granulomatous inflammatory disease. African ancestry may influence disease pathogenesis, as African-Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1384 highly ancestry-informative single-nucleotide polymorphisms genotyped on 1357 sarcoidosis cases and 703 unaffected controls self-identified as African-American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)=1.90; P=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; P=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12, which had the most significant association with European ancestry (aRR=0.65; P=0.002), and markers on chromosomes 5p13 (aRR=1.46; P=0.005) and 5q31 (aRR=0.67; P=0.005), which correspond to regions we previously identified through sib-pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; P=2 × 10(-5)), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis.
authors.affiliation: Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI 48310, USA. brybick1@hfhs.org
authors.forename: B A
authors.initials: BA
authors.lastname: Rybicki
authors.forename: A M
authors.initials: AM
authors.lastname: Levin
authors.forename: P
authors.initials: P
authors.lastname: McKeigue
authors.forename: I
authors.initials: I
authors.lastname: Datta
authors.forename: C
authors.initials: C
authors.lastname: Gray-McGuire
authors.forename: M
authors.initials: M
authors.lastname: Colombo
authors.forename: D
authors.initials: D
authors.lastname: Reich
authors.forename: R R
authors.initials: RR
authors.lastname: Burke
authors.forename: M C
authors.initials: MC
authors.lastname: Iannuzzi
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics*; D044465:White People / Q000235:genetics