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

Elena Sánchez, Astrid Rasmussen, Laura Riba, Eduardo Acevedo-Vasquez, Jennifer A. Kelly, Carl D. Langefeld, Adrianne H. Williams, Julie T. Ziegler, Mary E. Comeau, Miranda C. Marion, Ignacio García-De La Torre, Marco A. Maradiaga-Ceceña, Mario H. Cardiel, Jorge A. Esquivel-Valerio, Jacqueline Rodriguez-Amado, José Francisco Moctezuma, Pedro Miranda, Carlos E. Perandones, Cecilia Castel, Hugo A. LabordePaula Alba, Jorge L. Musuruana, I. Annelise Goecke, Juan Manuel Anaya, Kenneth M. Kaufman, Adam Adler, Stuart B. Glenn, Elizabeth E. Brown, Graciela S. Alarcón, Robert P. Kimberly, Jeffrey C. Edberg, Luis M. Vilá, Lindsey A. Criswell, Gary S. Gilkeson, Timothy B. Niewold, Javier Martín, Timothy J. Vyse, Susan A. Boackle, Rosalind Ramsey-Goldman, R. Hal Scofield, Michelle Petri, Joan T. Merrill, John D. Reveille, Betty P. Tsao, Lorena Orozco, Vicente Baca, Kathy L. Moser, Patrick M. Gaffney, Judith A. James, John B. Harley, Teresa Tusié-Luna, Bernardo A. Pons-Estel, Chaim O. Jacob, Marta E. Alarcón-Riquelme

Research output: Contribution to journalArticle

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3687-3694
Number of pages8
JournalArthritis and rheumatism
Volume64
Issue number11
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Sánchez, E., Rasmussen, A., Riba, L., Acevedo-Vasquez, E., Kelly, J. A., Langefeld, C. D., Williams, A. H., Ziegler, J. T., Comeau, M. E., Marion, M. C., García-De La Torre, I., Maradiaga-Ceceña, M. A., Cardiel, M. H., Esquivel-Valerio, J. A., Rodriguez-Amado, J., Moctezuma, J. F., Miranda, P., Perandones, C. E., Castel, C., ... Alarcón-Riquelme, M. E. (2012). Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis and rheumatism, 64(11), 3687-3694. https://doi.org/10.1002/art.34650