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Associations of autozygosity with a broad range of human phenotypes

Clark, David W ; Prasad, Rashmi B LU ; Groop, Leif LU and Wilson, James F. (2019) In Nature Communications 10(1).
Abstract

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... (More)

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.

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; ; and
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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
10
issue
1
article number
4957
publisher
Nature Publishing Group
external identifiers
  • pmid:31673082
  • scopus:85074297784
ISSN
2041-1723
DOI
10.1038/s41467-019-12283-6
language
English
LU publication?
yes
id
673d0f2c-31e3-4a1d-8590-c463e479d317
date added to LUP
2019-11-03 17:28:32
date last changed
2024-06-27 08:08:43
@article{673d0f2c-31e3-4a1d-8590-c463e479d317,
  abstract     = {{<p>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 &gt;1.4 million individuals, we show that FROH is significantly associated (p &lt; 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.</p>}},
  author       = {{Clark, David W and Prasad, Rashmi B and Groop, Leif and Wilson, James F.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Associations of autozygosity with a broad range of human phenotypes}},
  url          = {{http://dx.doi.org/10.1038/s41467-019-12283-6}},
  doi          = {{10.1038/s41467-019-12283-6}},
  volume       = {{10}},
  year         = {{2019}},
}