Associations of autozygosity with a broad range of human phenotypes

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Clark , D W , Okada , Y , Moore , K H S , Mason , D , Pirastu , N , Gandin , I , Mattsson , H , Barnes , C L K , Lin , K , Zhao , J H , Deelen , P , Rohde , R , Schurmann , C , Guo , X , Giulianini , F , Zhang , W , Medina-Gomez , C , Karlsson , R , Bao , Y , Bartz , T M , Baumbach , C , Biino , G , Bixley , M J , Brumat , M , Chai , J-F , Corre , T , Cousminer , D L , Dekker , A M , Eccles , D A , Van Eijk , K R , Fuchsberger , C , Gao , H , Germain , M , Gordon , S D , de Haan , H G , Harris , S E , Hofer , E , Huerta-Chagoya , A , Igartua , C , Jansen , I E , Jia , Y , Kacprowski , T , Karlsson , T , Kleber , M E , Li , S A , Li-Gao , R , Mahajan , A , Matsuda , K , Meidtner , K , Meng , W , Montasser , M E , van der Most , P J , Munz , M , Nutile , T , Palviainen , T , Prasad , G , Prasad , R B , Priyanka , T D S , Rizzi , F , Salvi , E , Sapkota , B R , Shriner , D , Skotte , L , Smart , M C , Smith , A V , van der Spek , A , Spracklen , C N , Strawbridge , R J , Tajuddin , S M , Trompet , S , Turman , C , Verweij , N , Viberti , C , Wang , L , Warren , H R , Wootton , R E , Yanek , L R , Yao , J , Yousri , N A , Zhao , W , Adeyemo , A A , Afaq , S , Alberto Aguilar-Salinas , C , Akiyama , M , Albert , M L , Allison , M A , Alver , M , Aung , T , Azizi , F , Bentley , A R , Boeing , H , Boerwinkle , E , Borja , J B , de Borst , G J , Bottinger , E P , Broer , L , Campbell , H , Chanock , S , Chee , M-L , Chen , G , Chen , Y-D I , Chen , Z , Chiu , Y-F , Cocca , M , Collins , F S , Concas , M P , Corley , J , Cugliari , G , Van Dam , R M , Damulina , A , Daneshpour , M S , Day , F R , Delgado , G E , Dhana , K , Doney , A S F , Doerr , M , Doumatey , A P , Dzimiri , N , Ebenesersdottir , S S , Elliott , J , Elliott , P , Ewert , R , Felix , J F , Fischer , K , Freedman , B I , Girotto , G , Goel , A , Gogele , M , Goodarzi , M O , Graff , M , Granot-Hershkovitz , E , Grodstein , F , Guarrera , S , Gudbjartsson , D F , Guity , K , Gunnarsson , B , Guo , Y , Hagenaars , S P , Haiman , C A , Halevy , A , Harris , T B , Hedayati , M , van Heel , D A , Hirata , M , Hofer , I , Hsiung , C A , Huang , J , Hung , Y-J , Ikram , M A , Jagadeesan , A , Jousilahti , P , Kamatani , Y , Kanai , M , Kerrison , N D , Kessler , T , Khaw , K-T , Khor , C C , de Kleijn , D P V , Koh , W-P , Kolcic , I , Kraft , P , Kramer , B K , Kutalik , Z , Kuusisto , J , Langenberg , C , Launer , L J , Lawlor , D A , Lee , I-T , Lee , W-J , Lerch , M M , Li , L , Liu , J , Loh , M , London , S J , Loomis , S , Lu , Y , Luan , J , Magi , R , Manichaikul , A W , Manunta , P , Masson , G , Matoba , N , Mei , X W , Meisinger , C , Meitinger , T , Mezzavilla , M , Milani , L , Millwood , I Y , Momozawa , Y , Moore , A , Morange , P-E , Moreno-Macias , H , Mori , T A , Morrison , A C , Muka , T , Murakami , Y , Murray , A D , de Mutsert , R , Mychaleckyj , J C , Nalls , M A , Nauck , M , Neville , M J , Nolte , I M , Ong , K K , Orozco , L , Padmanabhan , S , Palsson , G , Pankow , J S , Pattaro , C , Pattie , A , Polasek , O , Poulter , N , Pramstaller , P P , Quintana-Murci , L , Räikkönen , K , Ralhan , S , Rao , D C , van Rheenen , W , Rich , S S , Ridker , P M , Rietveld , C A , Robino , A , van Rooij , F J A , Ruggiero , D , Saba , Y , Sabanayagam , C , Sabater-Lleal , M , Felicita Sala , C , Salomaa , V , Sandow , K , Schmidt , H , Scott , L J , Scott , W R , Sedaghati-Khayat , B , Sennblad , B , van Setten , J , Sever , P J , Sheu , W H-H , Shi , Y , Shrestha , S , Shukla , S R , Sigurdsson , J K , Sikka , T T , Singh , J R , Smith , B H , Stancakova , A , Stanton , A , Starr , J M , Stefansdottir , L , Straker , L , Sulem , P , Sveinbjornsson , G , Swertz , M A , Taylor , A M , Taylor , K D , Terzikhan , N , Tham , Y-C , Thorleifsson , G , Thorsteinsdottir , U , Tillander , A , Tracy , R P , Tusie-Luna , T , Tzoulaki , I , Vaccargiu , S , Vangipurapu , J , Veldink , J H , Vitart , V , Volker , U , Vuoksimaa , E , Wakil , S M , Waldenberger , M , Wander , G S , Wang , Y X , Wareham , N J , Wild , S , Yajnik , C S , Yuan , J-M , Zeng , L , Zhang , L , Zhou , J , Amin , N , Asselbergs , F W , Bakker , S J L , Becker , D M , Lehne , B , Bennett , D A , van den Berg , L H , Berndt , S I , Bharadwaj , D , Bielak , L F , Bochud , M , Boehnke , M , Bouchard , C , Bradfield , J P , Brody , J A , Campbell , A , Carmi , S , Caulfield , M J , Cesarini , D , Chambers , J C , Chandak , G R , Cheng , C-Y , Ciullo , M , Cornelis , M , Cusi , D , Smith , G D , Deary , I J , Dorajoo , R , van Duijn , C M , Ellinghaus , D , Erdmann , J , Eriksson , J G , Evangelou , E , Evans , M K , Faul , J D , Feenstra , B , Feitosa , M , Foisy , S , Franke , A , Friedlander , Y , Gasparini , P , Gieger , C , Gonzalez , C , Goyette , P , Grant , S F A , Griffiths , L R , Groop , L , Gudnason , V , Gyllensten , U , Hakonarson , H , Hamsten , A , van der Harst , P , Heng , C-K , Hicks , A A , Hochner , H , Huikuri , H , Hunt , S C , Jaddoe , V W V , De Jager , P L , Johannesson , M , Johansson , A , Jonas , J B , Jukema , J W , Junttila , J , Kaprio , J , Kardia , S L R , Karpe , F , Kumari , M , Laakso , M , van der Laan , S W , Lahti , J , Laudes , M , Lea , R A , Lieb , W , Lumley , T , Martin , N G , Marz , W , Matullo , G , McCarthy , M I , Medland , S E , Merriman , T R , Metspalu , A , Meyer , B F , Mohlke , K L , Montgomery , G W , Mook-Kanamori , D , Munroe , P B , North , K E , Nyholt , D R , O'connell , J R , Ober , C , Oldehinkel , A J , Palmas , W , Palmer , C , Pasterkamp , G G , Patin , E , Pennell , C E , Perusse , L , Peyser , P A , Pirastu , M , Polderman , T J C , Porteous , D J , Posthuma , D , Psaty , B M , Rioux , J D , Rivadeneira , F , Rotimi , C , Rotter , J I , Rudan , I , Den Ruijter , H M , Sanghera , D K , Sattar , N , Schmidt , R , Schulze , M B , Schunkert , H , Scott , R A , Shuldiner , A R , Sim , X , Small , N , Smith , J A , Sotoodehnia , N , Tai , E-S , Teumer , A , Timpson , N J , Toniolo , D , Tregouet , D-A , Tuomi , T , Vollenweider , P , Wang , C A , Weir , D R , Whitfield , J B , Wijmenga , C , Wong , T-Y , Wright , J , Yang , J , Yu , L , Zemel , B S , Zonderman , A B , Perola , M , Magnusson , P K E , Uitterlinden , A G , Kooner , J S , Chasman , D I , Loos , R J F , Franceschini , N , Franke , L , Haley , C S , Hayward , C , Walters , R G , Perry , J R B , Esko , T , Helgason , A , Stefansson , K , Joshi , P K , Kubo , M & Wilson , J F 2019 , ' Associations of autozygosity with a broad range of human phenotypes ' , Nature Communications , vol. 10 , 4957 . https://doi.org/10.1038/s41467-019-12283-6

Title: Associations of autozygosity with a broad range of human phenotypes
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; Alberto Aguilar-Salinas, Carlos; 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.; Doerr, Marcus; Doumatey, Ayo P.; Dzimiri, Nduna; Ebenesersdottir, S. Sunna; Elliott, Joshua; Elliott, Paul; Ewert, Ralf; Felix, Janine F.; Fischer, Krista; Freedman, Barry I.; Girotto, Giorgia; Goel, Anuj; Gogele, 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; Hofer, 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; Kramer, Bernhard K.; Kutalik, Zoltan; 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; Magi, Reedik; Manichaikul, Ani W.; Manunta, Paolo; Masson, Gisli; Matoba, Nana; Mei, Xue W.; Meisinger, Christa; Meitinger, Thomas; Mezzavilla, Massimo; Milani, Lili; Millwood, Iona Y.; Momozawa, Yukihide; Moore, Amy; Morange, Pierre-Emmanuel; Moreno-Macias, Hortensia; Mori, Trevor A.; Morrison, Alanna C.; Muka, Taulant; Murakami, Yoshinori; Murray, Alison D.; de Mutsert, Renee; Mychaleckyj, Josyf C.; Nalls, Mike A.; Nauck, Matthias; Neville, Matt J.; Nolte, Ilja M.; Ong, Ken K.; Orozco, Lorena; Padmanabhan, Sandosh; Palsson, 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; Felicita Sala, Cinzia; 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.; Stancakova, 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.; Tusie-Luna, Teresa; Tzoulaki, Ioanna; Vaccargiu, Simona; Vangipurapu, Jagadish; Veldink, Jan H.; Vitart, Veronique; Volker, 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, Asa; 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.; Marz, 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, Andre 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, Tonu; Helgason, Agnar; Stefansson, Kari; Joshi, Peter K.; Kubo, Michiaki; Wilson, James F.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Research Programs Unit
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, University Management
Date: 2019-10-31
Language: eng
Number of pages: 17
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/306985
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-ROH) for >1.4 million individuals, we show that F-ROH 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-ROH 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-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.
Subject: INBREEDING DEPRESSION
HOMOZYGOSITY
FERTILITY
LOCI
RUNS
QUANTIFICATION
3111 Biomedicine
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