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Associations of autozygosity with a broad range of human phenotypes

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posted on 2021-08-05, 12:49 authored by David W Clark, Alice V StantonAlice V Stanton, ROHgen consortium
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.


UK Medical Research Council Human Genetics Unit

MRC Doctoral Training Programme in Precision Medicine



The original article is available at

Published Citation

Clark DW, et al. Associations of autozygosity with a broad range of human phenotypes. Nat Commun. 2019;10(1):4957.

Publication Date

31 October 2019

PubMed ID



  • Beaumont Hospital
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology


Nature Publishing Group


  • Published Version (Version of Record)