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

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Sánchez, Elena
Rasmussen, Astrid
Riba, Laura
Acevedo?Vasquez, Eduardo
Kelly, Jennifer A.
Langefeld, Carl D.
Williams, Adrianne H.
Ziegler, Julie T.
Comeau, Mary E.
Marion, Miranda C.



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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 less than 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P less than 0.0001). American Indian ancestry protected against photosensitivity (P less than 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P less than 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P less than 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. Copyright © 2012 by the American College of Rheumatology.
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Africa , American Indian , Arthritis , Article , Asian , Demography , Discoid rash , Europe , Genetic analysis , Genetic association , Genetic risk , Genetic screening , Genotyping technique , Hematologic disease , Heredity , Human , Inflammation , Kidney disease , Major clinical study , Malar rash , Mouth ulcer , Neurologic disease , Onset age , Photosensitivity , Population genetics , Priority journal , Risk assessment , Skin disease , Systemic lupus erythematosus , Adolescent , Adult , Child , European Continental Ancestry Group , Female , Genetic Predisposition to Disease , Genotype , Humans , Indians , Indians , Lupus Erythematosus , Lupus Nephritis , Male , Middle Aged , Morbidity , Prevalence , Risk Factors , Socioeconomic Factors , Young Adult
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