Modeling the effects of consanguinity on autosomal and X-chromosomal runs of homozygosity and identity-by-descent sharing

Runs of homozygosity (ROH) and identity-by-descent (IBD) sharing can be studied in diploid coalescent models by noting that ROH and IBD-sharing at a genomic site are predicted to be inversely related to coalescence times-which in turn can be mathematically obtained in terms of parameters describing consanguinity rates. Comparing autosomal and X-chromosomal coalescent models, we consider ROH and IBD-sharing in relation to consanguinity that proceeds via multiple forms of first-cousin mating. We predict that across populations with different levels of consanguinity, (1) in a manner that is qualitatively parallel to the increase of autosomal IBD-sharing with autosomal ROH, X-chromosomal IBD-sharing increases with X-chromosomal ROH, owing to the dependence of both quantities on consanguinity levels; (2) even in the absence of consanguinity, X-chromosomal ROH and IBD-sharing levels exceed corresponding values for the autosomes, owing to the smaller population size and lower coalescence time for the X chromosome than for autosomes; (3) with matrilateral consanguinity, the relative increase in ROH and IBD-sharing on the X chromosome compared to the autosomes is greater than in the absence of consanguinity. Examining genome-wide SNPs in human populations for which consanguinity levels have been estimated, we find that autosomal and X-chromosomal ROH and IBD-sharing levels generally accord with the predictions. We find that each 1% increase in autosomal ROH is associated with an increase of 2.1% in X-chromosomal ROH, and each 1% increase in autosomal IBD-sharing is associated with an increase of 1.6% in X-chromosomal IBD-sharing. For each calculation, particularly for ROH, the estimate is reasonably close to the increase of 2% predicted by the population-size difference between autosomes and X chromosomes. The results support the utility of coalescent models for understanding patterns of genomic sharing and their dependence on sex-biased processes. Consanguinity in populations can give rise to long shared segments in pairs of genomes. This study compares autosomal and X-chromosomal levels of genomic sharing under a population-genetic model, examining shared segment lengths conditional on coalescence-time distributions. Four types of first-cousin consanguinity are considered. Using human population-genetic data, we find support for the model prediction that genomic sharing is greater on the X chromosome-which has a smaller population size-than on autosomes.

Automated summary

Runs of homozygosity (ROH) and identity-by-descent (IBD) sharing can be studied in diploid coalescent models. This study compares ROH and IBD sharing between autosomes and the X chromosome under different levels of consanguinity. The results support the prediction that genomic sharing is greater on the X chromosome due to its smaller population size. Coalescent models are useful for understanding patterns of genomic sharing dependent on sex-biased processes.