Associations of autozygosity with a broad range of human phenotypes
Authors: Clark David W , Okada Yukinori , Moore Kristjan H S , Mason Dan , Pirastu Nicola , Gandin Ilaria , Mattsson Hannele , Barnes Catriona L K , Lin Kuang , Zhao Jing Hua , Deelen Patrick , Rohde Rebecca , Schurmann Claudia , Guo Xiuqing , Giulianini Franco , Zhang Weihua , Medina-Gomez Carolina , Karlsson Robert , Bao Yanchun , Bartz Traci M , Baumbach Clemens , Biino Ginevra , Bixley Matthew J , Brumat Marco , Chai Jin-Fang , Corre Tanguy , Cousminer Diana L , Dekker Annelot M , Eccles David A , van Eijk Kristel R , Fuchsberger Christian , Gao He , Germain Marine , Gordon Scott D , de Haan Hugoline G , Harris Sarah E , Hofer Edith , Huerta-Chagoya Alicia , Igartua Catherine , Jansen Iris E , Jia Yucheng , Kacprowski Tim , Karlsson Torgny , Kleber Marcus E , Li Shengchao Alfred , Li-Gao Ruifang , Mahajan Anubha , Matsuda Koichi , Meidtner Karina , Meng Weihua , Montasser May E , van der Most Peter J , Munz Matthias , Nutile Teresa , Palviainen Teemu , Prasad Gauri , Prasad Rashmi B , Priyanka Tallapragada Divya Sri , Rizzi Federica , Salvi Erika , Sapkota Bishwa R , Shriner Daniel , Skotte Line , Smart Melissa C , Smith Albert Vernon , van der Spek Ashley , Spracklen Cassandra N , Strawbridge Rona J , Tajuddin Salman M , Trompet Stella , Turman Constance , Verweij Niek , Viberti Clara , Wang Lihua , Warren Helen R , Wootton Robyn E , Yanek Lisa R , Yao Jie , Yousri Noha A , Zhao Wei , Adeyemo Adebowale A , Afaq Saima , Aguilar-Salinas Carlos Alberto , Akiyama Masato , Albert Matthew L , Allison Matthew A , Alver Maris , Aung Tin , Azizi Fereidoun , Bentley Amy R , Boeing Heiner , Boerwinkle Eric , Borja Judith B , de Borst Gert J , Bottinger Erwin P , Broer Linda , Campbell Harry , Chanock Stephen , Chee Miao-Li , Chen Guanjie , Chen Yii-Der I , Chen Zhengming , Chiu Yen-Feng , Cocca Massimiliano , Collins Francis S , Concas Maria Pina , Corley Janie , Cugliari Giovanni , van Dam Rob M , Damulina Anna , Daneshpour Maryam S , Day Felix R , Delgado Graciela E , Dhana Klodian , Doney Alexander S F , Dörr Marcus , Doumatey Ayo P , Dzimiri Nduna , Ebenesersdóttir S Sunna , Elliott Joshua , Elliott Paul , Ewert Ralf , Felix Janine F , Fischer Krista , Freedman Barry I , Girotto Giorgia , Goel Anuj , Gögele Martin , Goodarzi Mark O , Graff Mariaelisa , Granot-Hershkovitz Einat , Grodstein Francine , Guarrera Simonetta , Gudbjartsson Daniel F , Guity Kamran , Gunnarsson Bjarni , Guo Yu , Hagenaars Saskia P , Haiman Christopher A , Halevy Avner , Harris Tamara B , Hedayati Mehdi , van Heel David A , Hirata Makoto , Höfer Imo , Hsiung Chao Agnes , Huang Jinyan , Hung Yi-Jen , Ikram M Arfan , Jagadeesan Anuradha , Jousilahti Pekka , Kamatani Yoichiro , Kanai Masahiro , Kerrison Nicola D , Kessler Thorsten , Khaw Kay-Tee , Khor Chiea Chuen , de Kleijn Dominique P V , Koh Woon-Puay , Kolcic Ivana , Kraft Peter , Krämer Bernhard K , Kutalik Zoltán , Kuusisto Johanna , Langenberg Claudia , Launer Lenore J , Lawlor Deborah A , Lee I-Te , Lee Wen-Jane , Lerch Markus M , Li Liming , Liu Jianjun , Loh Marie , London Stephanie J , Loomis Stephanie , Lu Yingchang , Luan Jian’an , Mägi Reedik , Manichaikul Ani W , Manunta Paolo , Másson Gísli , Matoba Nana , Mei Xue W , Meisinger Christa , Meitinger Thomas , Mezzavilla Massimo , Milani Lili , Millwood Iona Y , Momozawa Yukihide , Moore Amy , Morange Pierre-Emmanuel , Moreno-Macías Hortensia , Mori Trevor A , Morrison Alanna C , Muka Taulant , Murakami Yoshinori , Murray Alison D , de Mutsert Renée , Mychaleckyj Josyf C , Nalls Mike A , Nauck Matthias , Neville Matt J , Nolte Ilja M , Ong Ken K , Orozco Lorena , Padmanabhan Sandosh , Pálsson Gunnar , Pankow James S , Pattaro Cristian , Pattie Alison , Polasek Ozren , Poulter Neil , Pramstaller Peter P , Quintana-Murci Lluis , Räikkönen Katri , Ralhan Sarju , Rao Dabeeru C , van Rheenen Wouter , Rich Stephen S , Ridker Paul M , Rietveld Cornelius A , Robino Antonietta , van Rooij Frank J A , Ruggiero Daniela , Saba Yasaman , Sabanayagam Charumathi , Sabater-Lleal Maria , Sala Cinzia Felicita , Salomaa Veikko , Sandow Kevin , Schmidt Helena , Scott Laura J , Scott William R , Sedaghati-Khayat Bahareh , Sennblad Bengt , van Setten Jessica , Sever Peter J , Sheu Wayne H-H , Shi Yuan , Shrestha Smeeta , Shukla Sharvari Rahul , Sigurdsson Jon K , Sikka Timo Tonis , Singh Jai Rup , Smith Blair H , Stančáková Alena , Stanton Alice , Starr John M , Stefansdottir Lilja , Straker Leon , Sulem Patrick , Sveinbjornsson Gardar , Swertz Morris A , Taylor Adele M , Taylor Kent D , Terzikhan Natalie , Tham Yih-Chung , Thorleifsson Gudmar , Thorsteinsdottir Unnur , Tillander Annika , Tracy Russell P , Tusié-Luna Teresa , Tzoulaki Ioanna , Vaccargiu Simona , Vangipurapu Jagadish , Veldink Jan H , Vitart Veronique , Völker Uwe , Vuoksimaa Eero , Wakil Salma M , Waldenberger Melanie , Wander Gurpreet S , Wang Ya Xing , Wareham Nicholas J , Wild Sarah , Yajnik Chittaranjan S , Yuan Jian-Min , Zeng Lingyao , Zhang Liang , Zhou Jie , Amin Najaf , Asselbergs Folkert W , Bakker Stephan J L , Becker Diane M , Lehne Benjamin , Bennett David A , van den Berg Leonard H , Berndt Sonja I , Bharadwaj Dwaipayan , Bielak Lawrence F , Bochud Murielle , Boehnke Mike , Bouchard Claude , Bradfield Jonathan P , Brody Jennifer A , Campbell Archie , Carmi Shai , Caulfield Mark J , Cesarini David , Chambers John C , Chandak Giriraj Ratan , Cheng Ching-Yu , Ciullo Marina , Cornelis Marilyn , Cusi Daniele , Smith George Davey , Deary Ian J , Dorajoo Rajkumar , van Duijn Cornelia M , Ellinghaus David , Erdmann Jeanette , Eriksson Johan G , Evangelou Evangelos , Evans Michele K , Faul Jessica D , Feenstra Bjarke , Feitosa Mary , Foisy Sylvain , Franke Andre , Friedlander Yechiel , Gasparini Paolo , Gieger Christian , Gonzalez Clicerio , Goyette Philippe , Grant Struan F A , Griffiths Lyn R , Groop Leif , Gudnason Vilmundur , Gyllensten Ulf , Hakonarson Hakon , Hamsten Anders , van der Harst Pim , Heng Chew-Kiat , Hicks Andrew A , Hochner Hagit , Huikuri Heikki , Hunt Steven C , Jaddoe Vincent W V , De Jager Philip L , Johannesson Magnus , Johansson Åsa , Jonas Jost B , Jukema J Wouter , Junttila Juhani , Kaprio Jaakko , Kardia Sharon L. R. , Karpe Fredrik , Kumari Meena , Laakso Markku , van der Laan Sander W , Lahti Jari , Laudes Matthias , Lea Rodney A , Lieb Wolfgang , Lumley Thomas , Martin Nicholas G , März Winfried , Matullo Giuseppe , McCarthy Mark I , Medland Sarah E , Merriman Tony R , Metspalu Andres , Meyer Brian F , Mohlke Karen L , Montgomery Grant W , Mook-Kanamori Dennis , Munroe Patricia B , North Kari E , Nyholt Dale R , O’connell Jeffery R , Ober Carole , Oldehinkel Albertine J , Palmas Walter , Palmer Colin , Pasterkamp Gerard G , Patin Etienne , Pennell Craig E , Perusse Louis , Peyser Patricia A , Pirastu Mario , Polderman Tinca J. C. , Porteous David J , Posthuma Danielle , Psaty Bruce M , Rioux John D , Rivadeneira Fernando , Rotimi Charles , Rotter Jerome I , Rudan Igor , Den Ruijter Hester M , Sanghera Dharambir K , Sattar Naveed , Schmidt Reinhold , Schulze Matthias B , Schunkert Heribert , Scott Robert A , Shuldiner Alan R , Sim Xueling , Small Neil , Smith Jennifer A , Sotoodehnia Nona , Tai E-Shyong , Teumer Alexander , Timpson Nicholas J , Toniolo Daniela , Tregouet David-Alexandre , Tuomi Tiinamaija , Vollenweider Peter , Wang Carol A , Weir David R , Whitfield John B , Wijmenga Cisca , Wong Tien-Yin , Wright John , Yang Jingyun , Yu Lei , Zemel Babette S , Zonderman Alan B , Perola Markus , Magnusson Patrik K. E. , Uitterlinden André G , Kooner Jaspal S , Chasman Daniel I , Loos Ruth J. F. , Franceschini Nora , Franke Lude , Haley Chris S , Hayward Caroline , Walters Robin G , Perry John R. B. , Esko Tōnu , Helgason Agnar , Stefansson Kari , Joshi Peter K , Kubo Michiaki , Wilson James F 
Published: October 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 thatFROHis 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:FROHequivalent 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 ofFROHare confirmed within full-sibling pairs, where the variation inFROHis independent of all environmental confounding.