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Journal article
European Population Substructure Is Associated With Mucocutaneous Manifestations and Autoantibody Production in Systemic Lupus Erythematosus
Arthritis and rheumatism, v 60(8), pp 2448-2456
Aug 2009
PMID: 19644962
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Abstract
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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Details
- Title
- European Population Substructure Is Associated With Mucocutaneous Manifestations and Autoantibody Production in Systemic Lupus Erythematosus
- Creators
- Sharon A. Chung - University of California, San FranciscoChao Tian - University of California, DavisKimberly E. Taylor - University of California, San FranciscoAnnette T. Lee - Northwell HealthWard A. Ortmann - GenentechGeoffrey Hom - GenentechRobert R. Graham - GenentechJoanne Nititham - University of California, San FranciscoJennifer A. Kelly - Oklahoma Medical Research FoundationJean Morrisey - Oklahoma Medical Research FoundationHui Wu - University of California, Los AngelesHong Yin - Uppsala UniversityMarta E. Alarcon-Riquelme - Oklahoma Medical Research FoundationBetty P. Tsao - University of California, Los AngelesJohn B. Harley - University of OklahomaPatrick M. Gaffney - Oklahoma Medical Research FoundationKathy L. Moser - Oklahoma Medical Research FoundationSusan Manzi - University of PittsburghMichelle Petri - Johns Hopkins UniversityPeter K. Gregersen - Northwell HealthCarl D. Langefeld - Wake Forest UniversityTimothy W. Behrens - GenentechMichael F. Seldin - University of California, DavisLindsey A. Criswell - University of California, San Francisco
- Publication Details
- Arthritis and rheumatism, v 60(8), pp 2448-2456
- Publisher
- Wiley
- Number of pages
- 9
- Grant note
- Kirkland Scholar award 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 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Alliance for Lupus Research King Gustaf V's 80-Year Fund Wake Forest University Health Sciences Center for Public Health Genomics Torsten & Ragnar Soderbergs Foundation Swedish Research Council Knut and Alice Wallenberg Foundation through Royal Swedish Academy of Sciences; Knut & Alice Wallenberg Foundation Lupus Foundation of Minnesota Arthritis Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000268973600027
- Scopus ID
- 2-s2.0-68049085780
- Other Identifier
- 991021933899504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology