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. Bartz & 416 others Clemens 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, G. sli 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, T. nu Esko, Agnar Helgason, Kari Stefansson, Peter K. Joshi, Michiaki Kubo, James F. Wilson

Research output: Contribution to journalArticleAcademicpeer-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
Article number4957
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., ... Wilson, J. F. (2019). Associations of autozygosity with a broad range of human phenotypes. Nature Communications, 10(1), [4957]. https://doi.org/10.1038/s41467-019-12283-6
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, G. sli ; 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, T. nu ; Helgason, Agnar ; Stefansson, Kari ; Joshi, Peter K. ; Kubo, Michiaki ; Wilson, James F. / Associations of autozygosity with a broad range of human phenotypes. In: Nature Communications. 2019 ; Vol. 10, No. 1.
@article{0cb7d77bbab84bdc8d39d4724c806464,
title = "Associations of autozygosity with a broad range of human phenotypes",
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.",
author = "Clark, {David W.} and Yukinori Okada and Moore, {Kristjan H. S.} and Dan Mason and Nicola Pirastu and Ilaria Gandin and Hannele Mattsson and Barnes, {Catriona L. K.} and Kuang Lin and Zhao, {Jing Hua} and Patrick Deelen and Rebecca Rohde and Claudia Schurmann and Xiuqing Guo and Franco Giulianini and Weihua Zhang and Carolina Medina-Gomez and Robert Karlsson and Yanchun Bao and Bartz, {Traci M.} and Clemens Baumbach and Ginevra Biino and Bixley, {Matthew J.} and Marco Brumat and Jin-Fang Chai and Tanguy Corre and Cousminer, {Diana L.} and Dekker, {Annelot M.} and Eccles, {David A.} and {van Eijk}, {Kristel R.} and Christian Fuchsberger and He Gao and Marine Germain and Gordon, {Scott D.} and {de Haan}, {Hugoline G.} and Harris, {Sarah E.} and Edith Hofer and Alicia Huerta-Chagoya and Catherine Igartua and Jansen, {Iris E.} and Yucheng Jia and Tim Kacprowski and Torgny Karlsson and Kleber, {Marcus E.} and Li, {Shengchao Alfred} and Ruifang Li-Gao and Anubha Mahajan and Koichi Matsuda and Karina Meidtner and Weihua Meng and Montasser, {May E.} and {van der Most}, {Peter J.} and Matthias Munz and Teresa Nutile and Teemu Palviainen and Gauri Prasad and Prasad, {Rashmi B.} and Priyanka, {Tallapragada Divya Sri} and Federica Rizzi and Erika Salvi and Sapkota, {Bishwa R.} and Daniel Shriner and Line Skotte and Smart, {Melissa C.} and Smith, {Albert Vernon} and {van der Spek}, Ashley and Spracklen, {Cassandra N.} and Strawbridge, {Rona J.} and Tajuddin, {Salman M.} and Stella Trompet and Constance Turman and Niek Verweij and Clara Viberti and Lihua Wang and Warren, {Helen R.} and Wootton, {Robyn E.} and Yanek, {Lisa R.} and Jie Yao and Yousri, {Noha A.} and Wei Zhao and Adeyemo, {Adebowale A.} and Saima Afaq and Aguilar-Salinas, {Carlos Alberto} and Masato Akiyama and Albert, {Matthew L.} and Allison, {Matthew A.} and Maris Alver and Tin Aung and Fereidoun Azizi and Bentley, {Amy R.} and Heiner Boeing and Eric Boerwinkle and Borja, {Judith B.} and {de Borst}, {Gert J.} and Bottinger, {Erwin P.} and Linda Broer and Harry Campbell and Stephen Chanock and Miao-Li Chee and Guanjie Chen and Chen, {Yii-Der I.} and Zhengming Chen and Yen-Feng Chiu and Massimiliano Cocca and Collins, {Francis S.} and Concas, {Maria Pina} and Janie Corley and Giovanni Cugliari and {van Dam}, {Rob M.} and Anna Damulina and Daneshpour, {Maryam S.} and Day, {Felix R.} and Delgado, {Graciela E.} and Klodian Dhana and Doney, {Alexander S. F.} and Marcus D{\"o}rr and Doumatey, {Ayo P.} and Nduna Dzimiri and Ebenesersd{\'o}ttir, {S. Sunna} and Joshua Elliott and Paul Elliott and Ralf Ewert and Felix, {Janine F.} and Krista Fischer and Freedman, {Barry I.} and Giorgia Girotto and Anuj Goel and Martin G{\"o}gele and Goodarzi, {Mark O.} and Mariaelisa Graff and Einat Granot-Hershkovitz and Francine Grodstein and Simonetta Guarrera and Gudbjartsson, {Daniel F.} and Kamran Guity and Bjarni Gunnarsson and Yu Guo and Hagenaars, {Saskia P.} and Haiman, {Christopher A.} and Avner Halevy and Harris, {Tamara B.} and Mehdi Hedayati and {van Heel}, {David A.} and Makoto Hirata and Imo H{\"o}fer and Hsiung, {Chao Agnes} and Jinyan Huang and Yi-Jen Hung and Ikram, {M. Arfan} and Anuradha Jagadeesan and Pekka Jousilahti and Yoichiro Kamatani and Masahiro Kanai and Kerrison, {Nicola D.} and Thorsten Kessler and Kay-Tee Khaw and Khor, {Chiea Chuen} and {de Kleijn}, {Dominique P. V.} and Woon-Puay Koh and Ivana Kolcic and Peter Kraft and Kr{\"a}mer, {Bernhard K.} and Zolt{\'a}n Kutalik and Johanna Kuusisto and Claudia Langenberg and Launer, {Lenore J.} and Lawlor, {Deborah A.} and Lee, {I. Te} and Wen-Jane Lee and Lerch, {Markus M.} and Liming Li and Jianjun Liu and Marie Loh and London, {Stephanie J.} and Stephanie Loomis and Yingchang Lu and Jian’an Luan and Reedik M{\"a}gi and Manichaikul, {Ani W.} and Paolo Manunta and M{\'a}sson, {G. sli} and Nana Matoba and Mei, {Xue W.} and Christa Meisinger and Thomas Meitinger and Massimo Mezzavilla and Lili Milani and Millwood, {Iona Y.} and Yukihide Momozawa and Amy Moore and Pierre-Emmanuel Morange and Hortensia Moreno-Mac{\'i}as and Mori, {Trevor A.} and Morrison, {Alanna C.} and Taulant Muka and Yoshinori Murakami and Murray, {Alison D.} and {de Mutsert}, Ren{\'e}e and Mychaleckyj, {Josyf C.} and Nalls, {Mike A.} and Matthias Nauck and Neville, {Matt J.} and Nolte, {Ilja M.} and Ong, {Ken K.} and Lorena Orozco and Sandosh Padmanabhan and Gunnar P{\'a}lsson and Pankow, {James S.} and Cristian Pattaro and Alison Pattie and Ozren Polasek and Neil Poulter and Pramstaller, {Peter P.} and Lluis Quintana-Murci and Katri R{\"a}ikk{\"o}nen and Sarju Ralhan and Rao, {Dabeeru C.} and {van Rheenen}, Wouter and Rich, {Stephen S.} and Ridker, {Paul M.} and Rietveld, {Cornelius A.} and Antonietta Robino and {van Rooij}, {Frank J. A.} and Daniela Ruggiero and Yasaman Saba and Charumathi Sabanayagam and Maria Sabater-Lleal and Sala, {Cinzia Felicita} and Veikko Salomaa and Kevin Sandow and Helena Schmidt and Scott, {Laura J.} and Scott, {William R.} and Bahareh Sedaghati-Khayat and Bengt Sennblad and {van Setten}, Jessica and Sever, {Peter J.} and Sheu, {Wayne H. H.} and Yuan Shi and Smeeta Shrestha and Shukla, {Sharvari Rahul} and Sigurdsson, {Jon K.} and Sikka, {Timo Tonis} and Singh, {Jai Rup} and Smith, {Blair H.} and Alena Stanč{\'a}kov{\'a} and Alice Stanton and Starr, {John M.} and Lilja Stefansdottir and Leon Straker and Patrick Sulem and Gardar Sveinbjornsson and Swertz, {Morris A.} and Taylor, {Adele M.} and Taylor, {Kent D.} and Natalie Terzikhan and Yih-Chung Tham and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Annika Tillander and Tracy, {Russell P.} and Teresa Tusi{\'e}-Luna and Ioanna Tzoulaki and Simona Vaccargiu and Jagadish Vangipurapu and Veldink, {Jan H.} and Veronique Vitart and Uwe V{\"o}lker and Eero Vuoksimaa and Wakil, {Salma M.} and Melanie Waldenberger and Wander, {Gurpreet S.} and Wang, {Ya Xing} and Wareham, {Nicholas J.} and Sarah Wild and Yajnik, {Chittaranjan S.} and Jian-Min Yuan and Lingyao Zeng and Liang Zhang and Jie Zhou and Najaf Amin and Asselbergs, {Folkert W.} and Bakker, {Stephan J. L.} and Becker, {Diane M.} and Benjamin Lehne and Bennett, {David A.} and {van den Berg}, {Leonard H.} and Berndt, {Sonja I.} and Dwaipayan Bharadwaj and Bielak, {Lawrence F.} and Murielle Bochud and Mike Boehnke and Claude Bouchard and Bradfield, {Jonathan P.} and Brody, {Jennifer A.} and Archie Campbell and Shai Carmi and Caulfield, {Mark J.} and David Cesarini and Chambers, {John C.} and Chandak, {Giriraj Ratan} and Ching-Yu Cheng and Marina Ciullo and Marilyn Cornelis and Daniele Cusi and Smith, {George Davey} and Deary, {Ian J.} and Rajkumar Dorajoo and {van Duijn}, {Cornelia M.} and David Ellinghaus and Jeanette Erdmann and Eriksson, {Johan G.} and Evangelos Evangelou and Evans, {Michele K.} and Faul, {Jessica D.} and Bjarke Feenstra and Mary Feitosa and Sylvain Foisy and Andre Franke and Yechiel Friedlander and Paolo Gasparini and Christian Gieger and Clicerio Gonzalez and Philippe Goyette and Grant, {Struan F. A.} and Griffiths, {Lyn R.} and Leif Groop and Vilmundur Gudnason and Ulf Gyllensten and Hakon Hakonarson and Anders Hamsten and {van der Harst}, Pim and Chew-Kiat Heng and Hicks, {Andrew A.} and Hagit Hochner and Heikki Huikuri and Hunt, {Steven C.} and Jaddoe, {Vincent W. V.} and {de Jager}, {Philip L.} and Magnus Johannesson and {\AA}sa Johansson and Jonas, {Jost B.} and Jukema, {J. Wouter} and Juhani Junttila and Jaakko Kaprio and Kardia, {Sharon L. R.} and Fredrik Karpe and Meena Kumari and Markku Laakso and {van der Laan}, {Sander W.} and Jari Lahti and Matthias Laudes and Lea, {Rodney A.} and Wolfgang Lieb and Thomas Lumley and Martin, {Nicholas G.} and Winfried M{\"a}rz and Giuseppe Matullo and McCarthy, {Mark I.} and Medland, {Sarah E.} and Merriman, {Tony R.} and Andres Metspalu and Meyer, {Brian F.} and Mohlke, {Karen L.} and Montgomery, {Grant W.} and Dennis Mook-Kanamori and Munroe, {Patricia B.} and North, {Kari E.} and Nyholt, {Dale R.} and O’connell, {Jeffery R.} and Carole Ober and Oldehinkel, {Albertine J.} and Walter Palmas and Colin Palmer and Pasterkamp, {Gerard G.} and Etienne Patin and Pennell, {Craig E.} and Louis Perusse and Peyser, {Patricia A.} and Mario Pirastu and Polderman, {Tinca J. C.} and Porteous, {David J.} and Danielle Posthuma and Psaty, {Bruce M.} and Rioux, {John D.} and Fernando Rivadeneira and Charles Rotimi and Rotter, {Jerome I.} and Igor Rudan and {den Ruijter}, {Hester M.} and Sanghera, {Dharambir K.} and Naveed Sattar and Reinhold Schmidt and Schulze, {Matthias B.} and Heribert Schunkert and Scott, {Robert A.} and Shuldiner, {Alan R.} and Xueling Sim and Neil Small and Smith, {Jennifer A.} and Nona Sotoodehnia and Tai, {E. Shyong} and Alexander Teumer and Timpson, {Nicholas J.} and Daniela Toniolo and David-Alexandre Tregouet and Tiinamaija Tuomi and Peter Vollenweider and Wang, {Carol A.} and Weir, {David R.} and Whitfield, {John B.} and Cisca Wijmenga and Tien-Yin Wong and John Wright and Jingyun Yang and Lei Yu and Zemel, {Babette S.} and Zonderman, {Alan B.} and Markus Perola and Magnusson, {Patrik K. E.} and Uitterlinden, {Andr{\'e} G.} and Kooner, {Jaspal S.} and Chasman, {Daniel I.} and Loos, {Ruth J. F.} and Nora Franceschini and Lude Franke and Haley, {Chris S.} and Caroline Hayward and Walters, {Robin G.} and Perry, {John R. B.} and Esko, {T. nu} and Agnar Helgason and Kari Stefansson and Joshi, {Peter K.} and Michiaki Kubo and Wilson, {James F.}",
year = "2019",
doi = "10.1038/s41467-019-12283-6",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Clark, DW, Okada, Y, Moore, KHS, Mason, D, Pirastu, N, Gandin, I, Mattsson, H, Barnes, CLK, Lin, K, Zhao, JH, Deelen, P, Rohde, R, Schurmann, C, Guo, X, Giulianini, F, Zhang, W, Medina-Gomez, C, Karlsson, R, Bao, Y, Bartz, TM, Baumbach, C, Biino, G, Bixley, MJ, Brumat, M, Chai, J-F, Corre, T, Cousminer, DL, Dekker, AM, Eccles, DA, van Eijk, KR, Fuchsberger, C, Gao, H, Germain, M, Gordon, SD, de Haan, HG, Harris, SE, Hofer, E, Huerta-Chagoya, A, Igartua, C, Jansen, IE, Jia, Y, Kacprowski, T, Karlsson, T, Kleber, ME, Li, SA, Li-Gao, R, Mahajan, A, Matsuda, K, Meidtner, K, Meng, W, Montasser, ME, van der Most, PJ, Munz, M, Nutile, T, Palviainen, T, Prasad, G, Prasad, RB, Priyanka, TDS, Rizzi, F, Salvi, E, Sapkota, BR, Shriner, D, Skotte, L, Smart, MC, Smith, AV, van der Spek, A, Spracklen, CN, Strawbridge, RJ, Tajuddin, SM, Trompet, S, Turman, C, Verweij, N, Viberti, C, Wang, L, Warren, HR, Wootton, RE, Yanek, LR, Yao, J, Yousri, NA, Zhao, W, Adeyemo, AA, Afaq, S, Aguilar-Salinas, CA, Akiyama, M, Albert, ML, Allison, MA, Alver, M, Aung, T, Azizi, F, Bentley, AR, Boeing, H, Boerwinkle, E, Borja, JB, de Borst, GJ, Bottinger, EP, Broer, L, Campbell, H, Chanock, S, Chee, M-L, Chen, G, Chen, Y-DI, Chen, Z, Chiu, Y-F, Cocca, M, Collins, FS, Concas, MP, Corley, J, Cugliari, G, van Dam, RM, Damulina, A, Daneshpour, MS, Day, FR, Delgado, GE, Dhana, K, Doney, ASF, Dörr, M, Doumatey, AP, Dzimiri, N, Ebenesersdóttir, SS, Elliott, J, Elliott, P, Ewert, R, Felix, JF, Fischer, K, Freedman, BI, Girotto, G, Goel, A, Gögele, M, Goodarzi, MO, Graff, M, Granot-Hershkovitz, E, Grodstein, F, Guarrera, S, Gudbjartsson, DF, Guity, K, Gunnarsson, B, Guo, Y, Hagenaars, SP, Haiman, CA, Halevy, A, Harris, TB, Hedayati, M, van Heel, DA, Hirata, M, Höfer, I, Hsiung, CA, Huang, J, Hung, Y-J, Ikram, MA, Jagadeesan, A, Jousilahti, P, Kamatani, Y, Kanai, M, Kerrison, ND, Kessler, T, Khaw, K-T, Khor, CC, de Kleijn, DPV, Koh, W-P, Kolcic, I, Kraft, P, Krämer, BK, Kutalik, Z, Kuusisto, J, Langenberg, C, Launer, LJ, Lawlor, DA, Lee, IT, Lee, W-J, Lerch, MM, Li, L, Liu, J, Loh, M, London, SJ, Loomis, S, Lu, Y, Luan, J, Mägi, R, Manichaikul, AW, Manunta, P, Másson, GS, Matoba, N, Mei, XW, Meisinger, C, Meitinger, T, Mezzavilla, M, Milani, L, Millwood, IY, Momozawa, Y, Moore, A, Morange, P-E, Moreno-Macías, H, Mori, TA, Morrison, AC, Muka, T, Murakami, Y, Murray, AD, de Mutsert, R, Mychaleckyj, JC, Nalls, MA, Nauck, M, Neville, MJ, Nolte, IM, Ong, KK, Orozco, L, Padmanabhan, S, Pálsson, G, Pankow, JS, Pattaro, C, Pattie, A, Polasek, O, Poulter, N, Pramstaller, PP, Quintana-Murci, L, Räikkönen, K, Ralhan, S, Rao, DC, van Rheenen, W, Rich, SS, Ridker, PM, Rietveld, CA, Robino, A, van Rooij, FJA, Ruggiero, D, Saba, Y, Sabanayagam, C, Sabater-Lleal, M, Sala, CF, Salomaa, V, Sandow, K, Schmidt, H, Scott, LJ, Scott, WR, Sedaghati-Khayat, B, Sennblad, B, van Setten, J, Sever, PJ, Sheu, WHH, Shi, Y, Shrestha, S, Shukla, SR, Sigurdsson, JK, Sikka, TT, Singh, JR, Smith, BH, Stančáková, A, Stanton, A, Starr, JM, Stefansdottir, L, Straker, L, Sulem, P, Sveinbjornsson, G, Swertz, MA, Taylor, AM, Taylor, KD, Terzikhan, N, Tham, Y-C, Thorleifsson, G, Thorsteinsdottir, U, Tillander, A, Tracy, RP, Tusié-Luna, T, Tzoulaki, I, Vaccargiu, S, Vangipurapu, J, Veldink, JH, Vitart, V, Völker, U, Vuoksimaa, E, Wakil, SM, Waldenberger, M, Wander, GS, Wang, YX, Wareham, NJ, Wild, S, Yajnik, CS, Yuan, J-M, Zeng, L, Zhang, L, Zhou, J, Amin, N, Asselbergs, FW, Bakker, SJL, Becker, DM, Lehne, B, Bennett, DA, van den Berg, LH, Berndt, SI, Bharadwaj, D, Bielak, LF, Bochud, M, Boehnke, M, Bouchard, C, Bradfield, JP, Brody, JA, Campbell, A, Carmi, S, Caulfield, MJ, Cesarini, D, Chambers, JC, Chandak, GR, Cheng, C-Y, Ciullo, M, Cornelis, M, Cusi, D, Smith, GD, Deary, IJ, Dorajoo, R, van Duijn, CM, Ellinghaus, D, Erdmann, J, Eriksson, JG, Evangelou, E, Evans, MK, Faul, JD, Feenstra, B, Feitosa, M, Foisy, S, Franke, A, Friedlander, Y, Gasparini, P, Gieger, C, Gonzalez, C, Goyette, P, Grant, SFA, Griffiths, LR, Groop, L, Gudnason, V, Gyllensten, U, Hakonarson, H, Hamsten, A, van der Harst, P, Heng, C-K, Hicks, AA, Hochner, H, Huikuri, H, Hunt, SC, Jaddoe, VWV, de Jager, PL, Johannesson, M, Johansson, Å, Jonas, JB, Jukema, JW, Junttila, J, Kaprio, J, Kardia, SLR, Karpe, F, Kumari, M, Laakso, M, van der Laan, SW, Lahti, J, Laudes, M, Lea, RA, Lieb, W, Lumley, T, Martin, NG, März, W, Matullo, G, McCarthy, MI, Medland, SE, Merriman, TR, Metspalu, A, Meyer, BF, Mohlke, KL, Montgomery, GW, Mook-Kanamori, D, Munroe, PB, North, KE, Nyholt, DR, O’connell, JR, Ober, C, Oldehinkel, AJ, Palmas, W, Palmer, C, Pasterkamp, GG, Patin, E, Pennell, CE, Perusse, L, Peyser, PA, Pirastu, M, Polderman, TJC, Porteous, DJ, Posthuma, D, Psaty, BM, Rioux, JD, Rivadeneira, F, Rotimi, C, Rotter, JI, Rudan, I, den Ruijter, HM, Sanghera, DK, Sattar, N, Schmidt, R, Schulze, MB, Schunkert, H, Scott, RA, Shuldiner, AR, Sim, X, Small, N, Smith, JA, Sotoodehnia, N, Tai, ES, Teumer, A, Timpson, NJ, Toniolo, D, Tregouet, D-A, Tuomi, T, Vollenweider, P, Wang, CA, Weir, DR, Whitfield, JB, Wijmenga, C, Wong, T-Y, Wright, J, Yang, J, Yu, L, Zemel, BS, Zonderman, AB, Perola, M, Magnusson, PKE, Uitterlinden, AG, Kooner, JS, Chasman, DI, Loos, RJF, Franceschini, N, Franke, L, Haley, CS, Hayward, C, Walters, RG, Perry, JRB, Esko, TN, Helgason, A, Stefansson, K, Joshi, PK, Kubo, M & Wilson, JF 2019, 'Associations of autozygosity with a broad range of human phenotypes' Nature Communications, vol. 10, no. 1, 4957. https://doi.org/10.1038/s41467-019-12283-6

Associations of autozygosity with a broad range of human phenotypes. / 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, G. sli; 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, T. nu; Helgason, Agnar; Stefansson, Kari; Joshi, Peter K.; Kubo, Michiaki; Wilson, James F.

In: Nature Communications, Vol. 10, No. 1, 4957, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Associations of autozygosity with a broad range of human phenotypes

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AU - Okada, Yukinori

AU - Moore, Kristjan H. S.

AU - Mason, Dan

AU - Pirastu, Nicola

AU - Gandin, Ilaria

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AU - Kumari, Meena

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AU - Lieb, Wolfgang

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AU - Martin, Nicholas G.

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AU - Metspalu, Andres

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AU - Mohlke, Karen L.

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AU - Mook-Kanamori, Dennis

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AU - Perusse, Louis

AU - Peyser, Patricia A.

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AU - Polderman, Tinca J. C.

AU - Porteous, David J.

AU - Posthuma, Danielle

AU - Psaty, Bruce M.

AU - Rioux, John D.

AU - Rivadeneira, Fernando

AU - Rotimi, Charles

AU - Rotter, Jerome I.

AU - Rudan, Igor

AU - den Ruijter, Hester M.

AU - Sanghera, Dharambir K.

AU - Sattar, Naveed

AU - Schmidt, Reinhold

AU - Schulze, Matthias B.

AU - Schunkert, Heribert

AU - Scott, Robert A.

AU - Shuldiner, Alan R.

AU - Sim, Xueling

AU - Small, Neil

AU - Smith, Jennifer A.

AU - Sotoodehnia, Nona

AU - Tai, E. Shyong

AU - Teumer, Alexander

AU - Timpson, Nicholas J.

AU - Toniolo, Daniela

AU - Tregouet, David-Alexandre

AU - Tuomi, Tiinamaija

AU - Vollenweider, Peter

AU - Wang, Carol A.

AU - Weir, David R.

AU - Whitfield, John B.

AU - Wijmenga, Cisca

AU - Wong, Tien-Yin

AU - Wright, John

AU - Yang, Jingyun

AU - Yu, Lei

AU - Zemel, Babette S.

AU - Zonderman, Alan B.

AU - Perola, Markus

AU - Magnusson, Patrik K. E.

AU - Uitterlinden, André G.

AU - Kooner, Jaspal S.

AU - Chasman, Daniel I.

AU - Loos, Ruth J. F.

AU - Franceschini, Nora

AU - Franke, Lude

AU - Haley, Chris S.

AU - Hayward, Caroline

AU - Walters, Robin G.

AU - Perry, John R. B.

AU - Esko, T. nu

AU - Helgason, Agnar

AU - Stefansson, Kari

AU - Joshi, Peter K.

AU - Kubo, Michiaki

AU - Wilson, James F.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074297784&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31673082

U2 - 10.1038/s41467-019-12283-6

DO - 10.1038/s41467-019-12283-6

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4957

ER -

Clark DW, Okada Y, Moore KHS, Mason D, Pirastu N, Gandin I et al. Associations of autozygosity with a broad range of human phenotypes. Nature Communications. 2019;10(1). 4957. https://doi.org/10.1038/s41467-019-12283-6