Journal Article

Associations of autozygosity with a broad range of human phenotypes

Kumari, Meena, Broer, Linda, IRCCS San Raffaele Scientific Institute [Milan, Italie], Clinical Institute of Medical and Chemical Laboratory Diagnostics ; Universität Graz = University of Graz, Doney, Alexander, Hirata, Makoto, Zonderman, Alan, Räikkönen, Katri, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam ; Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Chen, Yii-Der, Wakil, Salma, Straker, Leon, Nutile, Teresa, Génétique Evolutive Humaine - Human Evolutionary Genetics ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Patin, Etienne, Hedayati, Mehdi, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Division of Cancer Control and Population Sciences ; University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Pirastu, Mario, Li, Shengchao Alfred, Amin, Najaf, Brody, Jennifer, Freeman Hospital, van Der Spek, Ashley, National Research Council of Italy | Consiglio Nazionale

2019

Overview

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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 631/208/1397 / 631/208/205 / 631/208/721 / 631/208/730 / Alleles / Basic Medicine / Blood pressure / Body Size / Body Size - genetics / Breeding success / Children / Cognition / Consanguinity / Estimates / Fertility / Fertility - genetics / Genealogy / Genetic diversity / Genetic variance / Genomes / Haplotype / Haplotypes / Health Status / Homozygosity / Homozygote / Humanities and Social Sciences / Humans / Inbreeding / Inbreeding Depression / Inbreeding Depression - genetics / Life Sciences / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / multidisciplinary / Offspring / Phenotypes / Reproduction / Risk-Taking / Santé publique et épidémiologie / Science / Science (multidisciplinary) / Social factors / Tumor necrosis factor-TNF