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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‐Gómez, Robert Karlsson, Yanchun Bao, Traci M. Bartz, Clemens Baumbach, Ginevra Biino, Matthew J. Bixley, Marco Brumat, Jin Fang Chai, Tanguy Corre, Diana L. Cousminer, Annelot M. Dekker, David 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 Smart, Albert V. 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 Adeyemo, Saima Afaq, Carlos A. Aguilar‐Salinas, Masato Akiyama, Matthew L. Albert, Matthew Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R. Bentley, Heiner Boeing, Eric Boerwinkle, Judith B. Borja, Gert J. de Borst, Erwin P. Böttinger, Linda Broer, Harry Campbell, Stephen J. Chanock, Miao-Li Chee, Guanjie Chen, Yii‐Der Ida 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, Alex 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, Daníel F. Guðbjartsson, 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 A. Hsiung, Jinyan Huang, Yi‐Jen Hung, M. Arfan Ikram, Anuradha Jagadeesan, Yoichiro Kamatani, Masahiro Kanai, Nicola D. Kerrison, Thorsten Kessler, Kay‐Tee Khaw, Chiea Chuen Khor, Dominique P.V. de Kleijn, Woon‐Puay Koh, Ivana Kolčić, Peter Kraft, Bernhard Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J. Launer, Debbie 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 Manichaikul, Paolo Manunta, Gísli 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 Polašek, Neil R Poulter, Peter P. Pramstaller, Lluís Quintana‐Murci, Katri Räikkönen, Sarju Ralhan, D. 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 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 Shukla, Jon K. Sigurdsson, Timo Tõnis Sikka, Jai Rup Singh, Blair H. Smith, Alena Stančáková, Alice Stanton, John M. Starr, Lilja Stefánsdóttir, Leon Straker, Patrick Sulem, Garðar Sveinbjörnsson, Morris A. Swertz, Adele Taylor, Kent D. Taylor, Natalie Terzikhan, Yih Chung Tham, Guðmar Þorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P. Tracy, Teresa Tusié‐Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H. Veldink, Véronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M. Wakil, Mélanie Waldenberger, Gurpreet Singh Wander, Ya Xing Wang, Nicholas J. Wareham, Sarah H. 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 R. Chandak, Ching‐Yu Cheng, Marina Ciullo, Marilyn C. Cornelis, Daniele Cusi, George Davey Smith, Ian J. Deary, Rajkumar Dorajoo, Cornelia M. van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G. Eriksson, Εvangelos Εvangelou, Michele K. Evans, Jessica D. Faul, Bjarke Feenstra, Mary F. Feitosa, Sylvain Foisy, André Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio González, Philippe Goyette, Struan F.A. Grant, Lyn R. Griffiths, Leif Groop, Vilmundur Guðnason, Ulf Gyllensten, Håkon Håkonarson, Anders Hamsten, Pim van der Harst, Chew‐Kiat Heng, Andrew A. Hicks, Hagit Hochner, Heikki V. Huikuri, Steven C Hunt, Vincent W. V. Jaddoe, Philip L. De Jager, Magnus Johannesson, Åsa Johansson, Jost B. Jonas, J. 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Smith, Nona Sotoodehnia, E Shyong Tai, Alexander Teumer, Nicholas J. Timpson, Daniela Toniolo, David‐Alexandre Trégouët, Péter Vollenweider, Carol A. Wang, David R. Weir, John B. Whitfield, Cisca Wijmenga, Tien Yin Wong, John Wright, Jingyun Yang, Lei Yu, 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 Haley, Caroline Hayward, Robin Walters, John R. B. Perry, Tõnu Esko, Agnar Helgason, Kāri Stefánsson, Peter K. Joshi, Michiaki Kubo, James F. Wilson
Bibliographic record
VenueNature Communications · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and phenotypic traits in livestock
Canadian institutionsUniversité LavalMontreal Heart InstituteUniversité de MontréalCentre for Global Health Research
FundersNational Heart, Lung, and Blood InstituteNational Institute on AgingEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEconomic and Social Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesBiotechnology and Biological Sciences Research CouncilMedical Research CouncilWellcome TrustAgence Nationale de la RechercheNational Institute for Health and Care ResearchBritish Heart FoundationNational Cancer InstituteCancer Research UK
KeywordsInbreeding depressionRuns of HomozygosityInbreedingBiologyGeneticsOffspringFertilityConfoundingSiblingOdds ratioPopulationDemographyGenotypeGeneMedicinePregnancySingle-nucleotide polymorphismInternal medicine
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.968
Threshold uncertainty score0.704
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.047
GPT teacher head0.351
Teacher spread0.303 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations182
Published2019
Admission routes1
Has abstractyes