Associations of autozygosity with a broad range of human phenotypes

Alison D. Murray, David W. Clark (Corresponding Author), Okada Yukinori, Moore Kristjan H S, Dan Mason, Nicola N Pirastu, ROHgen consortium

Research output: Contribution to journalArticle

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 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.
Original languageEnglish
Article number4957
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 31 Oct 2019

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phenotype
Phenotype
Inbreeding
social factors
fertility
Reproduction
Fertility
Siblings
Parents
coefficients
Inbreeding Depression

Keywords

  • Breeding Success
  • Reproduction
  • genetic variance
  • Homozygosity
  • Social Factors
  • Phenotypes
  • Fertility
  • Inbreeding
  • Inbreeding depression
  • Progeny
  • Offspring
  • Children
  • QUANTIFICATION
  • LOCI
  • RUNS
  • FERTILITY
  • HOMOZYGOSITY
  • INBREEDING DEPRESSION

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Murray, A. D., Clark, D. W., Yukinori, O., Kristjan H S, M., Mason, D., Pirastu, N. N., & consortium, ROH. (2019). Associations of autozygosity with a broad range of human phenotypes. Nature Communications, 10, [4957]. https://doi.org/10.1038/s41467-019-12283-6

Associations of autozygosity with a broad range of human phenotypes. / Murray, Alison D.; Clark, David W. (Corresponding Author); Yukinori, Okada ; Kristjan H S, Moore; Mason, Dan; Pirastu, Nicola N; consortium, ROHgen .

In: Nature Communications, Vol. 10, 4957, 31.10.2019.

Research output: Contribution to journalArticle

Murray, AD, Clark, DW, Yukinori, O, Kristjan H S, M, Mason, D, Pirastu, NN & consortium, ROH 2019, 'Associations of autozygosity with a broad range of human phenotypes', Nature Communications, vol. 10, 4957. https://doi.org/10.1038/s41467-019-12283-6
Murray AD, Clark DW, Yukinori O, Kristjan H S M, Mason D, Pirastu NN et al. Associations of autozygosity with a broad range of human phenotypes. Nature Communications. 2019 Oct 31;10. 4957. https://doi.org/10.1038/s41467-019-12283-6
Murray, Alison D. ; Clark, David W. ; Yukinori, Okada ; Kristjan H S, Moore ; Mason, Dan ; Pirastu, Nicola N ; consortium, ROHgen . / Associations of autozygosity with a broad range of human phenotypes. In: Nature Communications. 2019 ; Vol. 10.
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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 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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