An ancestry informative marker set which recapitulates the known fine structure of populations in South Asia

Ranajit Das, Priyanka Upadhyai

The inference of genomic ancestry using ancestry informative markers (AIMs) can be useful for a range of studies in evolutionary genetics, biomedical research and forensic analyses. However, the determination of AIMs for highly admixed populations with complex ancestries has remained a formidable challenge. Given the immense genetic heterogeneity and unique population structure of the Indian subcontinent, here we sought to derive AIMs that would yield a cohesive and faithful understanding of South Asian genetic origins. To discern the most optimal strategy for extracting AIMs for South Asians we compared three commonly used AIMs-determining methods namely, Infocalc, FST, and Smart Principal Component Analysis (Smart PCA) with ADMIXTURE, using previously published whole genome data from the Indian subcontinent. Our findings suggest that the Infocalc approach is likely most suitable for delineation of South Asian AIMs. In particular, Infocalc-2,000 (N = 2000) appeared as the most informative South Asian AIMs panel that recapitulated the finer structure within South Asian genomes with high degree of sensitivity and precision, whereas a negative control with an equivalent number of randomly selected markers when used to interrogate the South Asian populations, failed to do so. We discuss the utility of all approaches under evaluation for AIMs derivation and interpreting South Asian genomic ancestries. Notably this is the first report of an AIMs panel for South Asian ancestry inference. Overall these findings may aid in developing cost-effective resources for large-scale demographic analyses and foster expansion of our knowledge of human origins and disease, in the South Asian context.