The Effect of Consanguinity on Between-Individual Identity-by-Descent Sharing

Headnote

ABSTRACT Consanguineous unions increase the rate at which identical genomic segments are paired within individuals to produce runs of homozygosity (ROH). The extent to which such unions affect identity-by-descent (IBD) genomic sharing between rather than within individuals in a population, however, is not immediately evident from within-individual ROH levels. Using the fact that the time to the most recent common ancestor (T_MRCA) for a pair of genomes at a specific locus is inversely related to the extent of IBD sharing between the genomes in the neighborhood of the locus, we study IBD sharing for a pair of genomes sampled either within the same individual or in different individuals. We develop a coalescent model for a set of mating pairs in a diploid population, treating the fraction of consanguineous unions as a parameter. Considering mating models that include unions between sibs, first cousins, and nth cousins, we determine the effect of the consanguinity rate on the mean T_MRCA for pairs of lineages sampled either within the same individual or in different individuals. The results indicate that consanguinity not only increases ROH sharing between the two genomes within an individual, it also increases IBD sharing between individuals in the population, the magnitude of the effect increasing with the kinship coefficient of the type of consanguineous union. Considering computations of ROH and between-individual IBD in Jewish populations whose consanguinity rates have been estimated from demographic data, we find that, in accord with the theoretical results, increases in consanguinity and ROH levels inflate levels of IBD sharing between individuals in a population. The results contribute more generally to the interpretation of runs of homozygosity, IBD sharing between individuals, and the relationship between ROH and IBD.

KEYWORDS coalescent; consanguinity; identity by descent; runs of homozygosity; time to the most recent common ancestor

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CONSANGUINEOUS unions, in which mating pairs have a close genetic relationship, produce offspring whose two genomic copies have higher levels of identity-by-descent (IBD) sharing than is seen for corresponding offspring of nonconsanguineous unions. The offspring of consanguineous unions can inherit two copies of a segment of the genome from the same recent ancestor-a shared close relative of both mother and father-through separate maternal and paternal lines of descent. Because...