Admixture Mapping of Lipid Traits in Hispanic Americans

Area of Science:

• Genetics
• Population Genetics
• Genomic Medicine

Background:

• Admixture mapping is a powerful tool for identifying genetic variants associated with traits in admixed populations.
• Hispanic Americans represent a complex admixed group with diverse ancestral origins, making them ideal for admixture mapping studies.

Purpose of the Study:

• To perform admixture mapping in genetically admixed Hispanic Americans to identify genomic loci associated with lipid traits.
• To investigate the specific ancestral contributions to identified lipid trait associations.

Main Methods:

• Characterized fine-scale population structure in large multiethnic cohorts using reference panels.
• Inferred local ancestry in genetically admixed Hispanic Americans using RFMix2.
• Performed admixture mapping for lipid traits (LDL-C, HDL-C, total cholesterol, triglycerides) using linear mixed models.

Main Results:

• Identified significant associations between ancestry proportions and lipid traits at loci 11q12.2 (LDL-C), 2p23.3 (total cholesterol), and 11q23.3 (triglycerides) in the HCHS/SOL cohort.
• Replicated LDL-C and triglyceride loci in independent cohorts; total cholesterol locus showed suggestive replication.
• Found Native American ancestry driving LDL-C association and both Native American and Iberian ancestries contributing to triglyceride associations.

Conclusions:

• Admixture mapping successfully identified novel genomic loci influencing lipid traits in Hispanic Americans.
• The study highlights the importance of considering specific ancestral contributions to understand trait variations in admixed populations.