Associations of autozygosity with a broad range of human phenotypes

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

    Research output: Contribution to journalArticlepeer-review

    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.

    Original languageEnglish (US)
    Article number4957
    JournalNature communications
    Volume10
    Issue number1
    DOIs
    StatePublished - Dec 1 2019

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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