title: European genetic ancestry is associated with a decreased risk of lupus nephritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stanford University, Stanford, California, USA.
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Richman
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Taylor
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Chung
authors.forename: Laura
authors.initials: L
authors.lastname: Trupin
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Edward
authors.initials: E
authors.lastname: Yelin
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Annette
authors.initials: A
authors.lastname: Lee
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D006680:HLA Antigens