Opportunities and challenges of local ancestry in genetic association analyses.

Recently, admixed populations make up an increasing percentage of the US and global populations, and the admixture is not uniform over space or time or across genomes. Therefore, it becomes indispensable to evaluate local ancestry in addition to global ancestry to improve genetic epidemiological studies. Recent advances in representing human genome diversity, coupled with large-scale whole-genome sequencing initiatives and improved tools for local ancestry inference, have enabled studies to demonstrate that incorporating local ancestry information enhances both genetic association analyses and polygenic risk predictions. Along with the opportunities that local ancestry provides, there exist challenges preventing its full usage in genetic analyses. In this review, we first summarize methods for local ancestry inference and illustrate how local ancestry can be utilized in various analyses, including admixture mapping, association testing, and polygenic risk score construction. In addition, we discuss current challenges in research involving local ancestry, both in terms of the inference itself and its role in genetic association studies. We further pinpoint some future study directions and methodology development opportunities to help more effectively incorporate local ancestry in genetic analyses. It is worth the effort to pursue those future directions and address these analytical challenges because the appropriate use of local ancestry estimates could help mitigate inequality in genomic medicine and improve our understanding of health and disease outcomes.