Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations

Arthritis Rheum. 2012 Nov;64(11):3687-94. doi: 10.1002/art.34650.

Abstract

Objective: American Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.

Methods: A total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).

Results: The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.

Conclusion: In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • European Continental Ancestry Group / genetics*
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genotype
  • Humans
  • Indians, North American / genetics*
  • Indians, North American / statistics & numerical data
  • Indians, South American / genetics*
  • Indians, South American / statistics & numerical data
  • Lupus Erythematosus, Systemic / ethnology*
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Nephritis / ethnology
  • Lupus Nephritis / genetics
  • Male
  • Middle Aged
  • Morbidity
  • Prevalence
  • Risk Factors
  • Socioeconomic Factors
  • Young Adult

Grant support