
European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus
Author(s) -
Chung Sharon A.,
Tian Chao,
Taylor Kimberly E.,
Lee Annette T.,
Ortmann Ward A.,
Hom Geoffrey,
Graham Robert R.,
Nititham Joanne,
Kelly Jennifer A.,
Morrisey Jean,
Wu Hui,
Yin Hong,
AlarcónRiquelme Marta E.,
Tsao Betty P.,
Harley John B.,
Gaffney Patrick M.,
Moser Kathy L.,
Manzi Susan,
Petri Michelle,
Gregersen Peter K.,
Langefeld Carl D.,
Behrens Timothy W.,
Seldin Michael F.,
Criswell Lindsey A.
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24707
Subject(s) - medicine , autoantibody , odds ratio , mucocutaneous zone , quartile , population , immunology , lupus erythematosus , confidence interval , disease , antibody , environmental health
Objective To determine whether genetic substructure in European‐derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. Methods SLE patients of European descent (n = 1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north–south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. Results In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity ( P trend = 0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [OR high–low ] 1.64, 95% confidence interval [95% CI] 1.13–2.35) and discoid rash ( P trend = 0.014, OR high–low 1.93, 95% CI 0.98–3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies ( P trend = 1.6 × 10 −4 , OR high–low 0.46, 95% CI 0.30–0.69) and anti–double‐stranded DNA autoantibodies ( P trend = 0.017, OR high–low 0.67, 95% CI 0.46–0.96). Conclusion This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.