학술논문
Associations of autozygosity with a broad range of human phenotypes
Document Type
Author
Medina-Gomez, Carolina; Karlsson, Robert; Giulianini, Franco; Zhang, Weihua; Bao, Yanchun; Bartz, Traci M; Baumbach, Clemens; Biino, Ginevra; Bixley, Matthew J; Brumat, Marco; Chai, Jin-Fang; Corre, Tanguy; Cousminer, Diana L; Bennett, David A; van den Berg, Leonard H; Bharadwaj, Dwaipayan; Berndt, Sonja I; Clark, David W; Okada, Yukinori; Mason, Dan; Pirastu, Nicola; Gandin, Ilaria; Moore, Kristjan H S; Barnes, Catriona L K; Lin, Kuang; Mattsson, Hannele; Zhao, Jing Hua; Deelen, Patrick; Rohde, Rebecca; Schurmann, Claudia; Guo, Xiuqing; Gao, He; Germain, Marine; Dekker, Annelot M; Eccles, David A; van Eijk, Kristel R; Fuchsberger, Christian; Khaw, Kay-Tee; Khor, Chiea Chuen; de Kleijn, Dominique P V; Koh, Woon-Puay; Kolcic, Ivana; Lu, Yingchang; Luan, Jian'an; Mägi, Reedik; Manichaikul, Ani W; Manunta, Paolo; Adeyemo, Adebowale A; Afaq, Saima; Aguilar-Salinas, Carlos Alberto; Akiyama, Masato; Albert, Matthew L; Meitinger, Thomas; Másson, Gísli; Matoba, Nana; Mei, Xue W; Meisinger, Christa; Sennblad, Bengt; van Setten, Jessica; Sever, Peter J; Sheu, Wayne H-H; Shi, Yuan; Allison, Matthew A; Alver, Maris; Aung, Tin; Azizi, Fereidoun; Bentley, Amy R; Milani, Lili; Millwood, Iona Y; Momozawa, Yukihide; Moore, Amy; Mezzavilla, Massimo; Shrestha, Smeeta; Shukla, Sharvari Rahul; Sigurdsson, Jon K; Sikka, Timo Tonis; Singh, Jai Rup; Smith, Blair H; Boeing, Heiner; Boerwinkle, Eric; Borja, Judith B; de Borst, Gert J; Bottinger, Erwin P; Morange, Pierre-Emmanuel; Moreno-Macías, Hortensia; Mori, Trevor A; Morrison, Alanna C; Muka, Taulant; Stančáková, Alena; Stanton, Alice; Starr, John M; Stefansdottir, Lilja; Straker, Leon; Broer, Linda; Campbell, Harry; Chanock, Stephen; Chee, Miao-Li; Chen, Guanjie; Murakami, Yoshinori; Murray, Alison D; de Mutsert, Renée; Mychaleckyj, Josyf C; Nalls, Mike A; Amin, Najaf; Asselbergs, Folkert W; Bakker, Stephan J L; Becker, Diane M; Lehne, Benjamin; Chen, Yii-Der I; Chen, Zhengming; Chiu, Yen-Feng; Cocca, Massimiliano; Collins, Francis S; Nauck, Matthias; Neville, Matt J; Nolte, Ilja M; Tracy, Russell P; Tusié-Luna, Teresa; Tzoulaki, Ioanna; Vaccargiu, Simona; Vangipurapu, Jagadish; Concas, Maria Pina; Corley, Janie; Cugliari, Giovanni; van Dam, Rob M; Damulina, Anna; Pankow, James S; Pattaro, Cristian; Ong, Ken K; Orozco, Lorena; Padmanabhan, Sandosh; Pálsson, Gunnar; Waldenberger, Melanie; Wander, Gurpreet S; Wang, Ya Xing; Wareham, Nicholas J; Wild, Sarah; Kleber, Marcus E; Li, Shengchao Alfred; Li-Gao, Ruifang; Daneshpour, Maryam S; Day, Felix R; Delgado, Graciela E; Dhana, Klodian; Doney, Alexander S F; Pattie, Alison; Polasek, Ozren; Poulter, Neil; Pramstaller, Peter P; Quintana-Murci, Lluis; Sulem, Patrick; Sveinbjornsson, Gardar; Swertz, Morris A; Taylor, Adele M; Taylor, Kent D; Mahajan, Anubha; Matsuda, Koichi; Meidtner, Karina; Meng, Weihua; Montasser, May E; Dörr, Marcus; Doumatey, Ayo P; Dzimiri, Nduna; Ebenesersdóttir, S Sunna; Elliott, Joshua; Räikkönen, Katri; Ralhan, Sarju; Rao, Dabeeru C; van Rheenen, Wouter; Rich, Stephen S; Veldink, Jan H; Vitart, Veronique; Völker, Uwe; Vuoksimaa, Eero; Wakil, Salma M; Munz, Matthias; Nutile, Teresa; Palviainen, Teemu; Prasad, Gauri; van der Most, Peter J; Elliott, Paul; Ewert, Ralf; Felix, Janine F; Fischer, Krista; Freedman, Barry I; Ridker, Paul M; Rietveld, Cornelius A; Robino, Antonietta; van Rooij, Frank J A; Ruggiero, Daniela; Yajnik, Chittaranjan S; Yuan, Jian-Min; Zeng, Lingyao; Zhang, Liang; Zhou, Jie; Prasad, Rashmi B; Priyanka, Tallapragada Divya Sri; Rizzi, Federica; Salvi, Erika; Sapkota, Bishwa R; Girotto, Giorgia; Goel, Anuj; Gögele, Martin; Goodarzi, Mark O; Graff, Mariaelisa; Saba, Yasaman; Sabanayagam, Charumathi; Sabater-Lleal, Maria; Sala, Cinzia Felicita; Salomaa, Veikko; Terzikhan, Natalie; Tham, Yih-Chung; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tillander, Annika; Shriner, Daniel; Skotte, Line; Smart, Melissa C; Smith, Albert Vernon; van der Spek, Ashley; Granot-Hershkovitz, Einat; Grodstein, Francine; Guarrera, Simonetta; Gudbjartsson, Daniel F; Guity, Kamran; Sandow, Kevin; Schmidt, Helena; Scott, Laura J; Scott, William R; Sedaghati-Khayat, Bahareh; Gordon, Scott D; de Haan, Hugoline G; Harris, Sarah E; Hofer, Edith; Huerta-Chagoya, Alicia; Spracklen, Cassandra N; Strawbridge, Rona J; Tajuddin, Salman M; Trompet, Stella; Turman, Constance; Gunnarsson, Bjarni; Guo, Yu; Hagenaars, Saskia P; Haiman, Christopher A; Halevy, Avner; Jansen, Iris E; Jia, Yucheng; Kacprowski, Tim; Karlsson, Torgny; Igartua, Catherine; Verweij, Niek; Viberti, Clara; Harris, Tamara B; Hedayati, Mehdi; van Heel, David A; Hirata, Makoto; Höfer, Imo; Kraft, Peter; Krämer, Bernhard K; Kutalik, Zoltán; Kuusisto, Johanna; Langenberg, Claudia; Yanek, Lisa R; Yao, Jie; Wang, Lihua; Warren, Helen R; Wootton, Robyn E; Hsiung, Chao Agnes; Huang, Jinyan; Hung, Yi-Jen; Ikram, M Arfan; Jagadeesan, Anuradha; Launer, Lenore J; Lawlor, Deborah A; Lee, I-Te; Lee, Wen-Jane; Lerch, Markus M; Yousri, Noha A; Zhao, Wei; Jousilahti, Pekka; Kamatani, Yoichiro; Kanai, Masahiro; Kerrison, Nicola D; Kessler, Thorsten; Loomis, Stephanie; Li, Liming; Liu, Jianjun; Loh, Marie; London, Stephanie J; Dorajoo, Rajkumar; van Duijn, Cornelia M; Pirastu, Mario; Polderman, Tinca J C; Porteous, David J; Posthuma, Danielle; Psaty, Bruce M; Erdmann, Jeanette; Eriksson, Johan G; Evangelou, Evangelos; Evans, Michele K; Faul, Jessica D; Rioux, John D; Rivadeneira, Fernando; Rotimi, Charles; Rotter, Jerome I; Rudan, Igor; Feenstra, Bjarke; Feitosa, Mary; Foisy, Sylvain; Franke, Andre; Friedlander, Yechiel; Den Ruijter, Hester M; Sanghera, Dharambir K; Sattar, Naveed; Schmidt, Reinhold; Schulze, Matthias B; Gasparini, Paolo; Gieger, Christian; Gonzalez, Clicerio; Goyette, Philippe; Grant, Struan F A; Schunkert, Heribert; Scott, Robert A; Shuldiner, Alan R; Sim, Xueling; Small, Neil; Hakonarson, Hakon; Griffiths, Lyn R; Groop, Leif; Gudnason, Vilmundur; Gyllensten, Ulf; Smith, Jennifer A; Sotoodehnia, Nona; Tai, E-Shyong; Teumer, Alexander; Timpson, Nicholas J; Hamsten, Anders; van der Harst, Pim; Heng, Chew-Kiat; Hicks, Andrew A; Hochner, Hagit; Toniolo, Daniela; Tregouet, David-Alexandre; Tuomi, Tiinamaija; Vollenweider, Peter; Wang, Carol A; Huikuri, Heikki; Hunt, Steven C; Jaddoe, Vincent W V; De Jager, Philip L; Johannesson, Magnus; Weir, David R; Whitfield, John B; Wijmenga, Cisca; Wong, Tien-Yin; Wright, John; Johansson, Åsa; Jonas, Jost B; Jukema, J Wouter; Junttila, Juhani; Kaprio, Jaakko; Yang, Jingyun; Yu, Lei; Zemel, Babette S; Zonderman, Alan B; Perola, Markus; Kardia, Sharon L R; Karpe, Fredrik; Kumari, Meena; Laakso, Markku; van der Laan, Sander W; Magnusson, Patrik K E; Uitterlinden, André G; Kooner, Jaspal S; Chasman, Daniel I; Loos, Ruth J F; Lahti, Jari; Laudes, Matthias; Lea, Rodney A; Lieb, Wolfgang; Lumley, Thomas; Franceschini, Nora; Franke, Lude; Haley, Chris S; Hayward, Caroline; Walters, Robin G; Martin, Nicholas G; März, Winfried; Matullo, Giuseppe; McCarthy, Mark I; Medland, Sarah E; Perry, John R B; Esko, Tōnu; Helgason, Agnar; Stefansson, Kari; Joshi, Peter K; Bielak, Lawrence F; Bochud, Murielle; Boehnke, Mike; Merriman, Tony R; Metspalu, Andres; Meyer, Brian F; Mohlke, Karen L; Montgomery, Grant W; Kubo, Michiaki; Wilson, James F; Bouchard, Claude; Bradfield, Jonathan P; Brody, Jennifer A; Campbell, Archie; Carmi, Shai; Mook-Kanamori, Dennis; Munroe, Patricia B; North, Kari E; Nyholt, Dale R; O'connell, Jeffery R; Cheng, Ching-Yu; Caulfield, Mark J; Cesarini, David; Chambers, John C; Chandak, Giriraj Ratan; Ciullo, Marina; Cornelis, Marilyn; Cusi, Daniele; Smith, George Davey; Deary, Ian J; Ober, Carole; Oldehinkel, Albertine J; Palmas, Walter; Palmer, Colin; Ellinghaus, David; Pasterkamp, Gerard G; Patin, Etienne; Pennell, Craig E; Perusse, Louis; Peyser, Patricia A
Source
Nature Communications. 10(1)
Subject
Language
English
ISSN
2041-1723
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 (F) for >1.4 million individuals, we show that F 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: F 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 F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.