title: European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus.
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 (Ptrend=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 (Ptrend=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 (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96).
  
  
  CONCLUSIONS
  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.
authors: Division of Rheumatology, University of California, San Francisco, CA 94143-0500, USA. sharon.chung@ucsf.edu
authors: Sharon A
authors: SA
authors: Chung
authors: Chao
authors: C
authors: Tian
authors: Kimberly E
authors: KE
authors: Taylor
authors: Annette T
authors: AT
authors: Lee
authors: Ward A
authors: WA
authors: Ortmann
authors: Geoffrey
authors: G
authors: Hom
authors: Robert R
authors: RR
authors: Graham
authors: Joanne
authors: J
authors: Nititham
authors: Jennifer A
authors: JA
authors: Kelly
authors: Jean
authors: J
authors: Morrisey
authors: Hui
authors: H
authors: Wu
authors: Hong
authors: H
authors: Yin
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Betty P
authors: BP
authors: Tsao
authors: John B
authors: JB
authors: Harley
authors: Patrick M
authors: PM
authors: Gaffney
authors: Kathy L
authors: KL
authors: Moser
authors: Susan
authors: S
authors: Manzi
authors: Michelle
authors: M
authors: Petri
authors: Peter K
authors: PK
authors: Gregersen
authors: Carl D
authors: CD
authors: Langefeld
authors: Timothy W
authors: TW
authors: Behrens
authors: Michael F
authors: MF
authors: Seldin
authors: Lindsey A
authors: LA
authors: Criswell
mesh_terms: D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000150:complications / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D010641:Phenotype; D010787:Photosensitivity Disorders / Q000097:blood / Q000209:etiology / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D017153:Antibodies, Anticardiolipin