Identifying Rare Variant Associations in Admixed Populations.

An admixed population and its ancestral populations bear different burdens of a complex disease. The ancestral populations may have different haplotypes of deleterious alleles and thus ancestry-gene interaction can influence disease risk in the admixed population. Among admixed individuals, deleterious haplotypes and their ancestries are dependent and can provide non-redundant association information. Herein we propose a local ancestry boosted sum test (LABST) for identifying chromosomal blocks that harbor rare variants but have no ancestry switches. For such a stable ancestral block, our LABST exploits ancestry-gene interaction and the number of rare alleles therein. Under the null of no genetic association, the test statistic asymptotically follows a chi-square distribution with one degree of freedom (1-df). Our LABST properly controlled type I error rates under extensive simulations, suggesting that the asymptotic approximation was accurate for the null distribution of the test statistic. In terms of power for identifying rare variant associations, our LABST uniformly outperformed several famed methods under four important modes of disease genetics over a large range of relative risks. In conclusion, exploiting ancestry-gene interaction can boost statistical power for rare variant association mapping in admixed populations.