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

Genes & Immunity volume 12, pages 67–77 (2011)Cite this article

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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.

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Acknowledgements

We recognize the contributions of the NHLBI-funded ACCESS and SAGA research groups in original data collection efforts.

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Authors and Affiliations

  1. Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI, USA

    B A Rybicki, A M Levin & I Datta

  2. Public Health Sciences Section, University of Edinburgh Medical School, Edinburgh, Scotland, UK

    P McKeigue & M Colombo

  3. Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    C Gray-McGuire

  4. Department of Genetics, Harvard University Medical School, Boston, MA, USA

    D Reich

  5. Division of Pulmonary Critical Care Medicine, Henry Ford Hospital, Detroit, MI, USA

    R R Burke

  6. Department of Medicine, Upstate Medical University, Syracuse, NY, USA

    M C Iannuzzi

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  1. B A Rybicki
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Rybicki, B., Levin, A., McKeigue, P. et al. A genome-wide admixture scan for ancestry-linked genes predisposing to sarcoidosis in African-Americans. Genes Immun 12, 67–77 (2011). https://doi.org/10.1038/gene.2010.56

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