期刊
ARTHRITIS AND RHEUMATISM
卷 60, 期 8, 页码 2448-2456出版社
WILEY
DOI: 10.1002/art.24707
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资金
- NIH [R01-AR-043814, R37-Al-24717, R37-AR-62277, R01-AR-042460, P20-RR-020143, R01-Al-063274, R01-AR-052125, R01-AR-043274-13, R01-AR-46588, K24-AR-002213, UL1-RR-024153, R01-AR-043727, R01-Al-68759, R01-AR-050267, P60-AR-053308, R01-AR-052300, K24-AR-02175, P20-RR-015577, R01-Al-31584, N01-AR-12253, P50-AR-48940, R01-DE-015223, N01-AR-62277, P01-AR049084, M01 RR-00079, M01 RR-00052, M01-RR000056]
- American College of Rheumatology Research and Education Foundation
- Torsten & Ragnar Soderbergs Foundation
- Swedish Research Council
- King Gustaf V's 80-Year Fund
- Alliance for Lupus Research
- Swedish Association against Rheumatism
- Knut and Alice Wallenberg Foundation through Royal Swedish Academy of Sciences
- Lupus Foundation of Minnesota
- Arthritis Foundation
- International Consortium on the Genetics of Systemic Lupus Erythematosus
- Wake Forest University Health Sciences Center for Public Health Genomics
- Kirkland Scholar award
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 [ORhigh-low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (P-trend = 0.014, ORhigh-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 x 10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (P-trend = 0.017, ORhigh-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.
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