Associations of autozygosity with a broad range of human phenotypes

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

Ancient human mtDNA genotypes from England reveal lost variation over the last millennium

We analysed the historical genetic diversity of human populations in Europe at the mtDNA control region for 48 ancient Britons who lived between ca AD 300 and 1000, and compared these with 6320 modern mtDNA genotypes from England and across Europe and the Middle East. We found that the historical sample shows greater genetic diversity than for modern England and other modern populations, indicating the loss of diversity over the last millennium. The pattern of haplotypic diversity was clearly European in the ancient sample, representing each of the modern haplogroups. There was also increased representation of one of the ancient haplotypes in modern populations. We consider these results in the context of possible selection or stochastic processes