학술논문
Associations of autozygosity with a broad range of human phenotypes
Document Type
Original Paper
Author
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
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 (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.
Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.
Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.