Admixture mapping identifies an amerindian ancestry locus associated with albuminuria in hispanics in the United States

Abstract

Increased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequenciesamongtheancestralpopulations.Admixturemappinganalysis of 12,212HispanicCommunityHealth Study/Study of Latinos participants, using a linearmixedmodel, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome2, spanning q11.2-14.1 and notpreviously reported forUACR,isdrivenby a differencebetween Amerindian ancestry and theother twoancestries (P<5.7 × 10-5). Within this locus, two common variants located at the proapoptotic BCL2L11 gene associated with UACR: rs116907128 (allele frequency=0.14;P=1.531027) and rs586283 (Callele frequency=0.35;P=4.2×10-7). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is commonamong full-heritage Pima Indians (A allele frequency=0.54) but ismonomorphic in the 1000Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (P=0.01; n=1568).Our findingsprovideevidence for thepresenceof Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.