A test for deviations from expected genotype frequencies on the X chromosome for sex-biased admixed populations

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Genome-wide scans for deviations from expected genotype frequencies, as determined by the Hardy–Weinberg equilibrium (HWE), are commonly applied to detect genotyping errors and deviations from random mating. In contrast to the autosomes, genotype frequencies on the X chromosome do not reach HWE within a single generation. Instead, if allele frequencies in males and females initially differ, they oscillate for a few generations toward equilibrium. Allele frequency differences between the sexes are expected in populations that have experienced recent sex-biased admixture, namely, their male and female founders differed in ancestry. Sex-biased admixture does not allow testing for HWE on X, because deviations are naturally expected, even under random mating (post admixture) and error-free genotyping. In this paper, we develop a likelihood ratio test and a χ2 test to detect deviations from expected genotype frequencies on X, beyond natural deviations due to sex-biased admixture. We demonstrate by simulations that our tests are powerful for detecting deviations due to non-random mating, while at the same time they do not reject the null under historical sex-biased admixture and random mating thereafter. We also demonstrate that when applied to 1000 Genomes project populations, our likelihood ratio test rejects fewer SNPs than other tests, but we describe limitations in the interpretation of the results.

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We thank Alon Keinan for discussions. SC thanks the German–Israeli Foundation for Scientific Research and Development (GIF) grant I-2489-407.6/2017 and the Israel Science Foundation (ISF) grant 407/17.

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Correspondence to Shai Carmi.

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