A genome-wide admixture scan for ancestry-linked genes predisposing to sarcoidosis in African-Americans View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03

AUTHORS

Benjamin A. Rybicki, Albert M. Levin, Paul McKeigue, Indrani Datta, Courtney Gray-McGuire, Marco Colombo, David Reich, Robert R. Burke, Michael C. Iannuzzi

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. More... »

PAGES

67

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gene.2010.56

DOI

http://dx.doi.org/10.1038/gene.2010.56

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051242808

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21179114


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