Abstract

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n= 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. FivePRDM15SNPs and twoPPP1R12BSNPs were associate with COPD risk(p= 0.05 to 5 x 10(-4)) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacentPRDM15SNPs were associated with COPD risk in the lower PMA group(p= 10(-3)to 3.77 x 10(-8)). Our study is the first to report an association betweenPPP1R12Band COPD risk, as well as effect modification between ethnicity andPRDM15SNPs in determining COPD risk. Our results are biologically plausible given thatPPP1R12BandPRDM15are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.