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