Associations of autozygosity with a broad range of human phenotypes.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 31673082.
- Also identified by DOI 10.1038/s41467-019-12283-6 and PMC identifier 6823371.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (F<sub>ROH</sub>) for >1.4 million individuals, we show that F<sub>ROH</sub> 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: F<sub>ROH</sub> 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 F<sub>ROH</sub> are confirmed within full-sibling pairs, where the variation in F<sub>ROH</sub> is independent of all environmental confounding.
Medical subject headings
- Body Size
- Cognition
- Consanguinity
- Fertility
- Health Status
- Inbreeding Depression
- Risk-Taking