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European genetic ancestry is associated with a decreased risk of lupus nephritis
Author(s) -
Richman Ilana B.,
Taylor Kimberly E.,
Chung Sharon A.,
Trupin Laura,
Petri Michelle,
Yelin Edward,
Graham Robert R.,
Lee Annette,
Behrens Timothy W.,
Gregersen Peter K.,
Seldin Michael F.,
Criswell Lindsey A.
Publication year - 2012
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.34567
Subject(s) - ancestry informative marker , odds ratio , single nucleotide polymorphism , lupus nephritis , genetic genealogy , genome wide association study , medicine , genetic association , kidney disease , disease , genetic predisposition , immunology , genotype , genetics , biology , population , environmental health , gene
Objective African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. Methods This was a cross‐sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single‐nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Results Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82–0.87; P = 1.9 × 10 −30 ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease ( IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA–DRB1*0301 and DRB1*1501 ) did not substantively alter this relationship. Conclusion European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

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