Open AccessGenetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus
Author(s) -
Sanchez Elena,
Webb Ryan D.,
Rasmussen Astrid,
Kelly Jennifer A.,
Riba Laura,
Kaufman Kenneth M.,
Garciade la Torre Ignacio,
Moctezuma Jose F.,
MaradiagaCeceña Marco A.,
CardielRios Mario H.,
Acevedo Eduardo,
CuchoVenegas Mariano,
Garcia Mercedes A.,
Gamron Susana,
PonsEstel Bernardo A.,
Vasconcelos Carlos,
Martin Javier,
TusiéLuna Teresa,
Harley John B.,
Richardson Bruce,
Sawalha Amr H.,
AlarcónRiquelme Marta E.
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27753
Subject(s) - allele , single nucleotide polymorphism , ancestry informative marker , genetic genealogy , genetics , genetic association , biology , genotype , genome wide association study , genetic admixture , immunology , medicine , gene , population , environmental health
Objective To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). Methods Single‐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. Results A 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. Conclusion Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.