David W Clark, Yukinori Okada… Paul Elliott, James F Wilson – please see full text article for the full (very long) list of authors
Nature Communications volume 10, Article number: 4957 (2019)
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.
Understanding Causes of Disease
A key research priority will be to use health data in its multiple forms to understand the causes of disease and discover new targeted treatments rather than just addressing symptoms. Led by...
Chair in Epidemiology and Public Health Medicine at Imperial College London
Professor Paul Elliott trained in clinical medicine and epidemiology as a Wellcome Trust Clinical Fellow at St Mary’s Hospital London and the London School of Hygiene & Tropical Medicine. He...