Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus
Copyright policy )Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus
AbstractObjectiveTo assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).MethodsSingle‐nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.ResultsA meta‐analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome‐wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.ConclusionOur results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.
- University of Michigan–Ann Arbor United States
- Institute of Parasitology and Biomedicine "López-Neyra" Spain
- University of Michigan–Flint United States
- Secretaria de Salud Mexico
- University of Oklahoma Health Sciences Center United States
CD11b Antigen, OX40 Ligand, STAT4 Transcription Factor, Polymorphism, Single Nucleotide, Life and Medical Sciences, Latin America, Gene Frequency, Geriatrics, Risk Factors, Case-Control Studies, Health Sciences, Interferon Regulatory Factors, Linear Models, Humans, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, American Indian or Alaska Native
CD11b Antigen, OX40 Ligand, STAT4 Transcription Factor, Polymorphism, Single Nucleotide, Life and Medical Sciences, Latin America, Gene Frequency, Geriatrics, Risk Factors, Case-Control Studies, Health Sciences, Interferon Regulatory Factors, Linear Models, Humans, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, American Indian or Alaska Native
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