Associations of autozygosity with a broad range of human phenotypes

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 (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.

Quantifying the prevalence of assortative mating in a human population

“…Also, the fat tail on the right of the Froh curve indicate that the amount of individuals with a higher Froh than the median is substantial. The figure shows that for values of F > 0.01, the frequency of individuals diminishes markedly in the Biobank data, congruent with finding that extreme inbreeding is non-adaptive as shown elsewhere (3,15).…”

“…The Frnd distribution of random matches of identical alleles obtained with a Mont Carlo model, mimicking the outcome if all parents of the individuals engaged in random mating; and the Froh distribution of the inbreeding coefficient obtained from data in Biobank. Both are plotted in Figure 1a The figure shows that for values of F > 0.009, the frequency of individuals diminishes markedly in the Biobank data confirming that extreme inbreeding is non-adaptive (3,15).…”

Fine-scale population structure and demographic history of British Pakistanis

“…We used the --auto-winsize flag to guess the best window size based on the SNP density. For PLINK, we followed previous publications 103,104 and used the following parameters: --homozyg-window-snp 50 --homozyg-snp 50 --homozyg-kb 1500 --homozyggap 1000, --homozyg-density 50 --homozyg-window-missing 5 --homozyg-window-het 1.…”

The language and values of genetics: invited editorial on “letter to the editor: time to update the language of genetics from the 19th to the twenty-first century. A response to Schmidtke and Cornel” \by Small, Mason and Wright) (DOI: 10.1007/s12687-020-00467-3).

“…The Letter to the Editor of Small et al (2020) is timely, reminding us that language plays such a key role in displaying our values -making them apparent -even when they are not explicitly the topic of conversation. It is an elegant response to the stimulating grit provided by Schmidtke and Cornel (2020) and refers to the experiences of the authors in relation to their involvement mediating between families who participated in the Born in Bradford project and the findings of the much larger, meta-study reported by Clark et al (2019). The authors' team, in frequent contact with the local community, anticipates that the findings of the larger project might raise concerns not only intrinsically, because of what has been found and how it has been interpreted, but additionally from the language in which the findings are expressed.…”

“…"Inbreeding" is perhaps the most sensitive of the three words singled out by Small et al, and is addressed by them more fully than the other examples. This is likely to be because a substantial part of the community in Bradford practices customary consanguineous marriage and could see the findings of Clark et al (2019) as support for those opposed to consanguinity. It would be most unfortunate if a community felt itself as so under threat that it might withdraw from research looking into the causes of important medical problems.…”