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

Daniel J. Cotter, Alissa L. Severson, Jonathan T.L. Kang, Hormazd N. Godrej, Shai Carmi, Noah A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageAmerican English
JournalG3: Genes, Genomes, Genetics
Volume14
Issue number2
DOIs
StatePublished - 7 Feb 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.

Keywords

  • X chromosome
  • coalescent theory
  • consanguinity
  • identity by descent
  • runs of homozygosity

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