Háskóli ÍslandsUniversity of IcelandClark, David WOkada, YukinoriMoore, Kristjan H SMason, DanPirastu, NicolaGandin, IlariaMattsson, HanneleBarnes, Catriona L KLin, KuangZhao, Jing HuaDeelen, PatrickRohde, RebeccaSchurmann, ClaudiaGuo, XiuqingGiulianini, FrancoZhang, WeihuaMedina-Gomez, CarolinaKarlsson, RobertBao, YanchunBartz, Traci MBaumbach, ClemensBiino, GinevraBixley, Matthew JBrumat, MarcoChai, Jin-FangCorre, TanguyCousminer, Diana LDekker, Annelot MEccles, David Avan Eijk, Kristel RFuchsberger, ChristianGao, HeGermain, MarineGordon, Scott Dde Haan, Hugoline GHarris, Sarah EHofer, EdithHuerta-Chagoya, AliciaIgartua, CatherineJansen, Iris EJia, YuchengKacprowski, TimKarlsson, TorgnyKleber, Marcus ELi, Shengchao AlfredLi-Gao, RuifangMahajan, AnubhaMatsuda, KoichiMeidtner, KarinaMeng, WeihuaMontasser, May Evan der Most, Peter JMunz, MatthiasNutile, TeresaPalviainen, TeemuPrasad, GauriPrasad, Rashmi BPriyanka, Tallapragada Divya SriRizzi, FedericaSalvi, ErikaSapkota, Bishwa 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C.Porteous, David JPosthuma, DaniellePsaty, Bruce MRioux, John DRivadeneira, FernandoRotimi, CharlesRotter, Jerome IRudan, IgorDen Ruijter, Hester MSanghera, Dharambir KSattar, NaveedSchmidt, ReinholdSchulze, Matthias BSchunkert, HeribertScott, Robert AShuldiner, Alan RSim, XuelingSmall, NeilSmith, Jennifer ASotoodehnia, NonaTai, E-ShyongTeumer, AlexanderTimpson, Nicholas JToniolo, DanielaTregouet, David-AlexandreTuomi, TiinamaijaVollenweider, PeterWang, Carol AWeir, David RWhitfield, John BWijmenga, CiscaWong, Tien-YinWright, JohnYang, JingyunYu, LeiZemel, Babette SZonderman, Alan BPerola, MarkusMagnusson, Patrik K. E.Uitterlinden, André GKooner, Jaspal SChasman, Daniel ILoos, Ruth J. F.Franceschini, NoraFranke, LudeHaley, Chris SHayward, CarolineWalters, Robin GPerry, John R. B.Esko, TōnuHelgason, AgnarStefansson, KariJoshi, Peter KKubo, MichiakiWilson, James F2020-02-122020-02-122019-10-31Clark, D.W., Okada, Y., Moore, K.H.S. et al. Associations of autozygosity with a broad range of human phenotypes. Nat Commun 10, 4957 (2019). https://doi.org/10.1038/s41467-019-12283-62041-1723https://hdl.handle.net/20.500.11815/1529Publisher's version (útgefin grein).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.4957eninfo:eu-repo/semantics/openAccessConsanguinityGenetic association studyGenetic markersInbreedingSkyldleikaræktBlóðsifjarErfðarannsóknirinfo:eu-repo/semantics/articleNature Communications10.1038/s41467-019-12283-6