Associations of autozygosity with a broad range of human phenotypes.

Clark, David W; Okada, Yukinori; Moore, Kristjan H S; Mason, Dan; Pirastu, Nicola; Gandin, Ilaria; Mattsson, Hannele; Barnes, Catriona L K; Lin, Kuang; Zhao, Jing Hua; Deelen, Patrick; Rohde, Rebecca; Schurmann, Claudia; Guo, Xiuqing; Giulianini, Franco; Zhang, Weihua; Medina-Gomez, Carolina; Karlsson, Robert; Bao, Yanchun; Bartz, Traci M; ... (2019). Associations of autozygosity with a broad range of human phenotypes. Nature communications, 10(1), p. 4957. Nature Publishing Group 10.1038/s41467-019-12283-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Muka, Taulant

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

05 Nov 2019 15:43

Last Modified:

07 Nov 2019 09:13

Publisher DOI:

10.1038/s41467-019-12283-6

PubMed ID:

31673082

BORIS DOI:

10.7892/boris.134574

URI:

https://boris.unibe.ch/id/eprint/134574

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