Internal medicine

Sociology

Inbreeding

Population

Biology

Gene

Offspring

Genotype

Demography

Inbreeding depression

Odds ratio

Developmental psychology

Single-nucleotide polymorphism

Psychology

Runs of Homozygosity

Sibling

Pregnancy

Fertility

Confounding

Genetics

Medicine

Nature Communications

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 ROH ) for &gt;1.4 million individuals, we show that F ROH is significantly associated ( p &lt; 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 ROH 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 ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.

Associations of autozygosity with a broad range of human phenotypes