Associations of autozygosity with a broad range of human phenotypes.
David W ClarkYukinori OkadaKristjan Helgi Swerford MooreDan MasonNicola PirastuAntonietta RobinoHannele MattssonCatriona L K BarnesKuang LinJing Hua ZhaoPatrick DeelenRebecca RohdeClaudia SchurmannXiuqing GuoFranco GiulianiniWeihua ZhangCarolina Medina-GomezRobert KarlssonYanchun BaoTraci M BartzClemens BaumbachGinevra BiinoMatthew J BixleyMarco BrumatJin Fang ChaiTanguy CorreDiana L CousminerAnnelot M DekkerDavid A EcclesKristel R van EijkChristian FuchsbergerHe GaoMarine GermainScott D GordonHugoline G de HaanSarah E HarrisEdith HoferAlicia Huerta-ChagoyaCatherine IgartuaIris E JansenYucheng JiaTim KacprowskiTorgny KarlssonMarcus Edi KleberShengchao Alfred LiRuifang Li-GaoAnubha MahajanKoichi MatsudaKarina MeidtnerWeihua MengMay E MontasserPeter J van der MostMatthias MunzTeresa NutileTeemu PalviainenGauri PrasadRashmi B PrasadTallapragada Divya Sri PriyankaFederica RizziMirna AndelicBishwa R SapkotaDaniel ShrinerLine SkotteMelissa C SmartAlbert Vernon SmithAshley van der SpekCassandra N SpracklenRona Juliette StrawbridgeSalman M TajuddinStella TrompetConstance TurmanNiek VerweijClara VibertiLihua WangHelen R WarrenRobyn E WoottonLisa R YanekJie YaoNoha A YousriWei ZhaoAdebowale A AdeyemoSaima AfaqCarlos Alberto Aguilar-SalinasMasato AkiyamaMatthew L AlbertMatthew A AllisonMaris AlverTin AungFereidoun AziziAmy R BentleyHeiner BoeingEric BoerwinkleJudith B BorjaGert J de BorstErwin P BottingerLinda BroerHarry CampbellStephen J ChanockMiao-Li CheeGuanjie ChenYii-Der I ChenZhengming ChenYen-Feng ChiuMassimiliano CoccaFrancis S CollinsMaria Pina ConcasJanie CorleyGiovanni CugliariRob M van DamAnna DamulinaMaryam S DaneshpourFelix R DayGraciela E DelgadoKlodian DhanaAlexander S F DoneyMarcus DörrAyo P DoumateyNduna DzimiriS Sunna EbenesersdóttirJoshua ElliottPaul ElliottRalf EwertJanine F FelixKrista FischerBarry I FreedmanGiorgia GirottoAnuj GoelMartin GögeleMark O GoodarziMariaelisa GraffEinat Granot-HershkovitzFrancine GrodsteinSimonetta GuarreraDaníel F GuðbjartssonKamran GuityBjarni GunnarssonYu GuoSaskia P HagenaarsChristopher A HaimanAvner HalevyTamara B HarrisMehdi HedayatiDavid A van HeelMakoto HirataImo HöferChao Agnes HsiungJinyan HuangYi-Jen HungMohammad Arfan IkramAnuradha JagadeesanPekka JousilahtiYoichiro KamataniMasahiro KanaiNicola D KerrisonThorsten KesslerKay-Tee KhawChiea Chuen KhorDominique P V de KleijnWoon-Puay KohIvana KolčićPeter KraftBernhard K KrämerZoltán KutalikJohanna KuusistoClaudia LangenbergLenore J LaunerDeborah A LawlorI-Te LeeWen-Jane LeeMarkus M LerchLiming LiJian-Jun LiuMarie LohStephanie J LondonStephanie LoomisYingchang LuJian'an LuanReedik MägiAni W ManichaikulPaolo ManuntaGísli MássonNana MatobaWinnie Xue MeiChrista MeisingerThomas MeitingerMassimo MezzavillaLili A MilaniIona Y MillwoodYukihide MomozawaAmy MoorePierre-Emmanuel MorangeHortensia Moreno-MacíasTrevor A MoriAlanna C MorrisonTaulant MukaYoshinori MurakamiAlison D MurrayRenée de MutsertJosyf C MychaleckyiMike A NallsMatthias NauckMatthew J NevilleIlja Maria NolteKen K OngLorena OrozcoSandosh PadmanabhanGunnar PálssonJames S PankowCristian PattaroAlison PattieOzren PolasekNeil PoulterPeter P PramstallerLluis Quintana-MurciKatri RäikkönenSarju RalhanDabeeru C RaoWouter Van RheenenStephen S RichPaul M RidkerCornelius A RietveldAntonietta RobinoFrank J A van RooijDaniela RuggieroYasaman SabaSabanayagam CharumathiMaria Sabater-LlealCinzia Felicita SalaVeikko V SalomaaKevin SandowHelena SchmidtLaura J ScottWilliam R ScottBahareh Sedaghati-KhayatBengt SennbladJessica van SettenPeter J SeverWayne H-H SheuYuan ShiSmeeta ShresthaSharvari Rahul ShuklaJon K SigurdssonTimo Tonis SikkaJai Rup SinghBlair Hamilton SmithAlena Stančáková YaluriAlice V StantonJohn M StarrLilja StefansdottirLeon M StrakerPatrick SulemGardar SveinbjornssonMorris A SwertzAdele M TaylorKent D TaylorNatalie TerzikhanYih-Chung ThamGudmar ThorleifssonUnnur ThorsteinsdottirAnnika TillanderRussell P TracyTeresa Tusié-LunaJoanna TzoulakiSimona VaccargiuJagadish VangipurapuJan Herman VeldinkVeronique VitartLinus VölkerEero VuoksimaaSalma M WakilMelanie WaldenbergerGurpreet Singh WanderYa-Xing WangNicholas J WarehamSarah D WildChittaranjan S YajnikWoon-Puay KohLingyao ZengLiang ZhangJie ZhouNajaf AminFolkert W. AsselbergsStephan J L BakkerDiane M BeckerBenjamin LehneDavid A BennettLeonard H van den BergSonja I BerndtDwaipayan BharadwajLawrence F BielakMurielle BochudMichael BoehnkeClaude BouchardJonathan P BradfieldJennifer A BrodyArchie I CampbellShai CarmiMark J CaulfieldDavid CesariniJohn C ChambersGiriraj Ratan ChandakChing-Yu ChengMarina CiulloMarilyn CornelisDaniele CusiGeorge Davey SmithIan J DearyRajkumar DorajooCornelia M van DuijnDavid EllinghausJeanette ErdmannJohan G ErikssonEvangelos EvangelouMichele K EvansJessica D FaulBjarke FeenstraMary F FeitosaSylvain FoisyAndre FrankeYechiel FriedlanderPaolo GaspariniChristian GiegerClicerio GonzalezPhilippe GoyetteStruan F A GrantLyn R GriffithsLeif C GroopVilmundur G GudnasonUlf GyllenstenHakon HakonarsonAnders HamstenPim van der HarstChew-Kiat HengAndrew A HicksHagit HochnerHeikki HuikuriSteven C HuntVincent W V JaddoePhilip Lawrence De JagerMagnus JohannessonÅsa JohanssonJost Bruno JonasJohan Wouter JukemaJuhani JunttilaJaakko A KaprioSharon L R KardiaFredrik KarpeMeena KumariMarkku LaaksoSander W van der LaanJari M T LahtiMatthias LaudesRodney A LeaWolfgang LiebThomas LumleyNicholas G MartinWinfried MärzGiuseppe MatulloMark I McCarthySarah E MedlandTony Raymond MerrimanAndres MetspaluBrian F MeyerKaren L MohlkeGrant W MontgomeryDennis Mook-KanamoriPatricia B MunroeKari E NorthDale R NyholtJeffery R O'connellCarole OberAlbertine J OldehinkelWalter PalmasColin Neil Alexander PalmerGerard G PasterkampEtienne PatinCraig E PennellLouis PerussePatricia A PeyserMario PirastuTinca J C PoldermanDavid J PorteousDanielle PosthumaBruce M PsatyJohn D RiouxFernando RivadeneiraCharles N RotimiJerome I RotterIgor RudanHester M Den RuijterDharambir K SangheraNaveed SattarReinhold SchmidtMatthias B SchulzeHeribert SchunkertRobert A ScottAlan R ShuldinerXueling S SimNeil SmallJennifer A SmithNona SotoodehniaE-Shyong TaiAlexander TeumerNicholas John TimpsonDaniela TonioloDavid-Alexandre TregouetTiinamaija TuomiPeter VollenweiderCarol A WangDavid R WeirJohn B WhitfieldCisca WijmengaTien-Yin WongJohn WrightJingyun YangLei YuBabette S ZemelAlan B ZondermanMarkus PerolaPatrik K E MagnussonAndre G UitterlindenJaspal S KoonerDaniel I ChasmanRuth J F LoosNora FranceschiniLude H FrankeChristopher S HaleyCaroline HaywardRobin G WaltersJohn R B PerryTōnu EskoAgnar HelgasonKari StefanssonPeter K JoshiMichiaki KuboJames F WilsonPublished in: Nature communications (2019)
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.