European population substructure correlates with systemic lupus erythematosus endophenotypes in North Americans of European descent

I. B. Richman, S. A. Chung, K. E. Taylor, R. Kosoy, C. Tian, W. A. Ortmann, J. Nititham, A. T. Lee, S. Rutman, M. Petri, S. Manzi, T. W. Behrens, P. K. Gregersen, Michael F Seldin, L. A. Criswell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Previous work has demonstrated that Northern and Southern European ancestries are associated with specific systemic lupus erythematosus (SLE) manifestations. In this study, 1855 SLE cases of European descent were genotyped for 4965 single-nucleotide polymorphisms and principal components analysis of genotype information was used to define population substructure. The first principal component (PC1) distinguished Northern from Southern European ancestry, PC2 differentiated Eastern from Western European ancestry and PC3 delineated Ashkenazi Jewish ancestry. Compared with Northern European ancestry, Southern European ancestry was associated with autoantibody production (odds ratio (OR)1.40, 95% confidence interval (CI) 1.07-1.83) and renal involvement (OR 1.41, 95% CI 1.06-1.87), and was protective for discoid rash (OR0.51, 95% CI 0.32-0.82) and photosensitivity (OR0.74, 95% CI 0.56-0.97). Both serositis (OR1.46, 95% CI 1.12-1.89) and autoantibody production (OR1.38, 95% CI 1.06-1.80) were associated with Western compared to Eastern European ancestry. Ashkenazi Jewish ancestry was protective against neurologic manifestations of SLE (OR0.62, 95% CI 0.40-0.94). Homogeneous clusters of cases defined by multiple PCs demonstrated stronger phenotypic associations. Genetic ancestry may contribute to the development of SLE endophenotypes and should be accounted for in genetic studies of disease characteristics.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalGenes and Immunity
Volume11
Issue number6
DOIs
StatePublished - Sep 2010

Keywords

  • epidemiology
  • genetics
  • population substructure
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

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