Admixture Mapping of Lipid Traits in Hispanic Americans.

BACKGROUND: Admixture mapping can be leveraged to identify genomic loci associated with disease traits in admixed individuals such as Hispanic Americans. METHODS AND RESULTS: We characterized fine-scale population structure of participants (n=105 108) in the multiethnic eMERGE-III (electronic Medical Records and Genomics) cohort, using reference panels from the 1000 Genomes Project and a Native American cohort. We defined "genetically admixed Hispanic Americans" as those having ≥10% Native American genetic ancestry (n=5025), in addition to European (specifically, Iberian) and African genetic ancestry. This population descriptor was subsequently applied to 3 other cohorts: the MESA (Multi-Ethnic Study of Atherosclerosis; n=1176), WHI (Women's Health Initiative; n=2873), and the HCHS/SOL (Hispanic Community Health Study/Study of Latinos; n=7804). We inferred local ancestry along the genome in genetically admixed Hispanic Americans in each cohort using RFMix2 with phased haplotypes from SHAPEIT2. Local ancestry proportions were used for admixture mapping of lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) using extended linear mixed models that incorporated multiple or single ancestries. After accounting for fixed-effect covariates and random effects, ancestry proportions at the following loci were associated with lipid traits in the HCHS/SOL cohort: 11q12.2 (P=6.8×10-7) with low-density lipoprotein cholesterol, 2p23.3 (P=5.2×10-7) with total cholesterol, and 11q23.3 (P=7.3×10-12) with triglycerides. The LDL cholesterol and triglyceride loci replicated in at least one independent cohort, whereas the total cholesterol locus showed suggestive evidence for replication in the eMERGE cohort (P=0.073). Native American (NAMR) ancestry appeared to drive the LDL-C association, whereas both NAMR and Iberian population in Spain (IBS) ancestries contributed to the triglyceride signal. CONCLUSIONS: Admixture mapping in genetically admixed Hispanic Americans identified genomic loci influencing lipid traits and the different ancestral origins driving these associations.