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Nature Research, Nature Communications, 1(10), 2019

DOI: 10.1038/s41467-019-12283-6



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Associations of autozygosity with a broad range of human phenotypes

Journal article published in 2019 by David W. Clark ORCID, Yukinori Okada ORCID, Kristjan H. S. Moore ORCID, Dan Mason ORCID, Nicola Pirastu ORCID, Ilaria Gandin ORCID, Hannele Mattsson, Catriona L. K. Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen ORCID, Rebecca Rohde, Claudia Schurmann ORCID, Xiuqing Guo, Franco Giulianini and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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AbstractIn 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.