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Associations of autozygosity with a broad range of human phenotypes

David Clark 1 Yukinori Okada 2, 3, 4 Kristjan Moore 5 Dan Mason 6 Nicola Pirastu 1 Ilaria Gandin 7, 8 Hannele Mattsson Catriona Barnes 1 Kuang Lin Jing Hua Zhao 9 Patrick Deelen Rebecca Rohde Claudia Schurmann 10 Xiuqing Guo 11 Franco Giulianini 12 Weihua Zhang 13 Carolina Medina-Gomez Robert Karlsson 14 Yanchun Bao Traci Bartz Clemens Baumbach Ginevra Biino 15 Matthew Bixley Marco Brumat 8 Jin-Fang Chai Tanguy Corre 16 Diana Cousminer 17 Annelot Dekker David Eccles 18 Kristel van Eijk 19 Christian Fuchsberger 20 He Gao Marine Germain 21 Scott Gordon 22 Hugoline de Haan 23 Sarah Harris Edith Hofer 24 Alicia Huerta-Chagoya Catherine Igartua Iris Jansen 25 Yucheng Jia Tim Kacprowski Torgny Karlsson Marcus Kleber 26 Shengchao Alfred Li 27 Ruifang Li-Gao Anubha Mahajan 28 Koichi Matsuda Karina Meidtner 29 Weihua Meng May Montasser Peter van der Most 30 Matthias Munz Teresa Nutile 31 Teemu Palviainen Gauri Prasad Rashmi Prasad Tallapragada Divya Sri Priyanka Federica Rizzi Erika Salvi 32 Bishwa Sapkota Daniel Shriner Line Skotte Melissa Smart Albert Vernon Smith 33 Ashley van der Spek 34 Cassandra Spracklen Rona Strawbridge 35 Salman Tajuddin Stella Trompet 36 Constance Turman Niek Verweij 37 Clara Viberti Lihua Wang Helen Warren 38 Robyn Wootton Lisa Yanek 39 Jie Yao Noha Yousri Wei Zhao 40 Adebowale Adeyemo Saima Afaq Carlos Alberto Aguilar-Salinas Masato Akiyama 4 Matthew Albert 41, 42, 43 Matthew Allison Maris Alver 44 Tin Aung 45 Fereidoun Azizi Amy Bentley Heiner Boeing 46 Eric Boerwinkle 47 Judith Borja 48 Gert de Borst Erwin Bottinger 49 Linda Broer 50 Harry Campbell 1 Stephen Chanock 51 Miao-Li Chee Guanjie Chen Yii-Der Chen Zhengming Chen 52 Yen-Feng Chiu Massimiliano Cocca Francis Collins Maria Pina Concas Janie Corley Giovanni Cugliari Rob van Dam Anna Damulina Maryam Daneshpour Felix Day Graciela Delgado 53 Klodian Dhana Alexander Doney 54 Marcus Dörr 55 Ayo Doumatey Nduna Dzimiri S Sunna Ebenesersdóttir 5 Joshua Elliott 56 Paul Elliott 57 Ralf Ewert Janine Felix Krista Fischer 58 Barry Freedman 59 Giorgia Girotto 60, 8 Anuj Goel 61 Martin Gögele Mark Goodarzi Mariaelisa Graff Einat Granot-Hershkovitz Francine Grodstein 62 Simonetta Guarrera Daniel Gudbjartsson 5 Kamran Guity Bjarni Gunnarsson 5 Yu Guo 63 Saskia Hagenaars 64 Christopher Haiman 65 Avner Halevy Tamara Harris 66 Mehdi Hedayati David van Heel Makoto Hirata Imo Höfer Chao Agnes Hsiung Jinyan Huang Yi-Jen Hung M Arfan Ikram 67 Anuradha Jagadeesan 5 Pekka Jousilahti Yoichiro Kamatani 68, 4 Masahiro Kanai 69, 4 Nicola Kerrison Thorsten Kessler 5 Kay-Tee Khaw 70 Chiea Chuen Khor 71 Dominique de Kleijn 72 Woon-Puay Koh 45 Ivana Kolcic 73 Peter Kraft 74 Bernhard Krämer Zoltan Kutalik 75 Johanna Kuusisto 76 Claudia Langenberg 77 Lenore Launer 66 Deborah Lawlor I-Te Lee Wen-Jane Lee Markus Lerch Liming Li 78 Jianjun Liu 79 Marie Loh Stephanie London 80 Stephanie Loomis Yingchang Lu 81 Jian’an Luan 82 Reedik Mägi Ani Manichaikul Paolo Manunta Gísli Másson 5 Nana Matoba 4 Xue Mei 83 Christa Meisinger Thomas Meitinger 84 Massimo Mezzavilla Lili Milani 44 Iona Millwood Yukihide Momozawa Amy Moore 85 Pierre-Emmanuel Morange 86, 87 Hortensia Moreno-Macías Trevor Mori Alanna Morrison Taulant Muka Yoshinori Murakami Alison Murray 88 Renée de Mutsert 89 Josyf Mychaleckyj Mike Nalls 90 Matthias Nauck 91 Matt Neville Ilja Nolte 92 Ken Ong 93 Lorena Orozco Sandosh Padmanabhan 94 Gunnar Pálsson 5 James Pankow Cristian Pattaro Alison Pattie Ozren Polasek 95 Neil Poulter 96 Peter Pramstaller 95 Lluis Quintana-Murci 97, 98 Katri Räikkönen 17 Sarju Ralhan Dabeeru Rao Wouter van Rheenen 19 Stephen Rich Paul Ridker 99 Cornelius Rietveld 100 Antonietta Robino Frank van Rooij Daniela Ruggiero 31 Yasaman Saba Charumathi Sabanayagam Maria Sabater-Lleal Cinzia Felicita Sala Veikko Salomaa 101 Kevin Sandow Helena Schmidt 24 Laura Scott 102 William Scott Bahareh Sedaghati-Khayat Bengt Sennblad 103 Jessica van Setten 104 Peter Sever 96 Wayne H-H Sheu Yuan Shi 65 Smeeta Shrestha Sharvari Rahul Shukla Jon Sigurdsson 5 Timo Tonis Sikka Jai Rup Singh Blair Smith Alena Stančáková 76 Alice Stanton John Starr 1 Lilja Stefansdottir 105, 5 Leon Straker Patrick Sulem 50, 5 Gardar Sveinbjornsson 5 Morris Swertz 106 Adele Taylor Kent Taylor 107 Natalie Terzikhan Yih-Chung Tham Gudmar Thorleifsson 5 Unnur Thorsteinsdóttir 5 Annika Tillander Russell Tracy Teresa Tusié-Luna 108 Ioanna Tzoulaki 96 Simona Vaccargiu Jagadish Vangipurapu Jan Veldink 19 Veronique Vitart 109 Uwe Völker 110 Eero Vuoksimaa Salma Wakil Melanie Waldenberger 111 Gurpreet Wander Ya Xing Wang Nicholas Wareham 77 Sarah Wild Chittaranjan Yajnik 112 Jian-Min Yuan 113 Lingyao Zeng Liang Zhang 114 Jie Zhou 115 Najaf Amin 116 Folkert Asselbergs 117 Stephan Bakker Diane Becker Benjamin Lehne David Bennett 118 Leonard van den Berg 19 Sonja Berndt 119 Dwaipayan Bharadwaj Lawrence Bielak Murielle Bochud 120 Mike Boehnke Claude Bouchard 121 Jonathan Bradfield Jennifer Brody 122 Archie Campbell 1 Shai Carmi Mark Caulfield David Cesarini John Chambers 123 Giriraj Ratan Chandak Ching-Yu Cheng 124 Marina Ciullo 31 Marilyn Cornelis Daniele Cusi 32 George Davey Smith 125 Ian Deary 88 Rajkumar Dorajoo 126 Cornelia van Duijn 127 David Ellinghaus 128 Jeanette Erdmann 129 Johan Eriksson 17 Evangelos Evangelou 130 Michele Evans Jessica Faul 131 Bjarke Feenstra Mary Feitosa 132 Sylvain Foisy Andre Franke 133 Yechiel Friedlander Paolo Gasparini 134, 8 Christian Gieger 84 Clicerio Gonzalez Philippe Goyette Struan Grant Lyn Griffiths Leif Groop 135 Vilmundur Gudnason 136 Ulf Gyllensten 95 Hakon Hakonarson 137 Anders Hamsten 138 Pim van der Harst 92 Chew-Kiat Heng Andrew Hicks 139 Hagit Hochner Heikki Huikuri 140 Steven Hunt 141 Vincent Jaddoe 142 Philip de Jager 143 Magnus Johannesson Åsa Johansson 95 Jost Jonas 144 J Wouter Jukema 145 Juhani Junttila Jaakko Kaprio 146 Sharon Kardia 147 Fredrik Karpe 52 Meena Kumari 148 Markku Laakso 149 Sander van der Laan Jari Lahti 150 Matthias Laudes Rodney Lea Wolfgang Lieb 151 Thomas Lumley 152 Nicholas Martin 153 Winfried März 154 Giuseppe Matullo 155 Mark Mccarthy 156 Sarah Medland 157 Tony Merriman Andres Metspalu 44 Brian Meyer Karen Mohlke 158 Grant Montgomery 116 Dennis Mook-Kanamori Patricia Munroe Kari North 159 Dale Nyholt 17 Jeffery O’connell Carole Ober 160 Albertine Oldehinkel Walter Palmas Colin Palmer 54 Gerard Pasterkamp 161 Etienne Patin 97, 98 Craig Pennell Louis Pérusse 162 Patricia Peyser Mario Pirastu 163 Tinca Polderman David Porteous 1 Danielle Posthuma 164 Bruce Psaty 122 John Rioux Fernando Rivadeneira 165 Charles Rotimi 166 Jerome Rotter 167 Igor Rudan 95, 1 Hester den Ruijter Dharambir Sanghera Naveed Sattar 168 Reinhold Schmidt 88 Matthias Schulze 169 Heribert Schunkert 129 Robert Scott 170 Alan Shuldiner 171 Xueling Sim 172 Neil Small Jennifer Smith Nona Sotoodehnia E-Shyong Tai Alexander Teumer 50 Nicholas Timpson 173 Daniela Toniolo 174 David-Alexandre Trégouët 175, 176 Tiinamaija Tuomi Peter Vollenweider 177 Carol Wang David Weir 178 John Whitfield 157 Cisca Wijmenga 179 Tien-Yin Wong 180 John Wright 6 Jingyun Yang 88 Lei Yu 181 Babette Zemel Alan Zonderman Markus Perola 182 Patrik Magnusson 183 André Uitterlinden 50 Jaspal Kooner Daniel Chasman 99 Ruth Loos 170 Nora Franceschini 159 Lude Franke 184 Chris Haley Caroline Hayward 95 Robin Walters 185 John Perry 186 Tōnu Esko Agnar Helgason 5 Kari Stefansson 5 Peter Joshi 1 Michiaki Kubo James Wilson 187, 1, *
* Corresponding author
1 University of Edinburgh
2 BROAD INSTITUTE - Broad Institute of MIT and Harvard
3 Osaka University Graduate School of Medicine
4 RIKEN IMS - Laboratory for Cardiovascular Genomics and Informatics [Yokohama]
5 deCODE genetics [Reykjavik]
6 BTHFT - Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK]
7 Area Science Park
8 University of Trieste
9 MRC Epidemiology Unit, Institute of Metabolic Science
10 Interfaculty Institute for Genetics and Functional Genomics
11 Harbor UCLA Medical Center [Torrance, Ca.]
12 Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA
13 ECE - Department of Electrical and Computer Engineering [Waterloo]
14 MEB - Department of Medical Epidemiology and Biostatistics
15 Institute of Pop. Genetics, CNR, Sassari;Shardna life science Pula Cagliari
16 SIB - Swiss Institute of Bioinformatics [Lausanne]
17 Medstar Research Institute
18 FSU - Florida State University [Tallahassee]
19 University Medical Center [Utrecht]
20 Centre for Population Health Sciences
21 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition
22 California State University [Sacramento]
23 Department of Thrombosis and Haemostasis
24 Medical University Graz
25 Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam
26 Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg
27 FNLCR - Frederick National Laboratory for Cancer Research
28 Wellcome Trust Centre of Human Genetics, University of Oxford
29 Department of Epidemiology
30 UMCG - University Medical Center Groningen [Groningen]
31 Institute of Genetics and Biophysics
32 Department of Medicine, Surgery, and Dentistry
33 Icelandic Heart Association, Kopavogur, Iceland.
34 Department of Epidemiology [Rotterdam]
35 University of Glasgow
36 Department of Cardiology, Leiden University Medical Center, Leiden
37 Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA,
38 QMUL - Queen Mary University of London
39 General Internal Medicine, Johns Hopkins School of Medicine
40 IBMP - Institut de biologie moléculaire des plantes
41 Immunobiologie des Cellules dendritiques
42 CRT - Centre de Recherche Translationnelle
43 Genentech, Inc.
44 University of Tartu
45 Duke-NUS Medical School [Singapore]
46 DifE - Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
47 Human Genome Sequencing Center, Baylor College of Medicine
48 University of San Carlos
49 MSSM - Icahn School of Medicine at Mount Sinai [New York]
50 King‘s College London
51 Division of Cancer Epidemiology and Genetics
52 University of Oxford [Oxford]
53 Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg
54 Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee
55 Department of Internal Medicine B, University Medicine Greifswald, Greifswald
56 University of Chicago
57 University of Huddersfield
58 Infectious diseases division, Department of internal medicine
59 Department of Internal Medicine - Section on Nephrology [Winston-Salem, NC, USA]
60 Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste
61 Radcliffe Department of Medicine [Oxford]
62 Department of Epidemiology
63 KMUST - Kunming University of Science and Technology
64 sans affiliation
65 USC - University of Southern California
66 NIA - National Institute on Aging [Bethesda, USA]
67 Erasmus MC - Erasmus University Medical Center [Rotterdam]
68 CNG - Centre National de Génotypage
69 Osaka University Graduate School of Medicine
70 MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival
71 NUS - National University of Singapore
72 ECL - Experimental Cardiology Laboratory
73 Department of Medical Statistics, Epidemiology and Medical Informatics
74 Department of Epidemiology
75 Department of Medical Genetics
76 Department of Medicine
77 MRC Epidemiology Unit
78 Capital Normal University [Beijing]
79 Saw Swee Hock School of Public Health
80 National Institute for Environmental Health Sciences Research Triangle Park
81 Brown University
82 MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge
83 Toyota Research Institute
84 HZM - Helmholtz-Zentrum München
85 Department of Chemistry and Biochemistry [Boulder]
86 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
87 TIMONE - Hôpital de la Timone [CHU - APHM]
88 Metacohorts Consortium
89 Leiden University Medical Center (LUMC)
90 NIH - National Institutes of Health [Bethesda]
91 Institute of Clinical Chemistry and Laboratory Medicine
92 University of Groningen [Groningen]
93 Medical Research Concil Epidemiology Unit
94 Faculty of Medicine
95 Genetics and Pathology
96 Imperial College London
97 Génétique Evolutive Humaine - Human Evolutionary Genetics
98 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
99 Brigham and Women's Hospital [Boston]
100 Erasmus University Rotterdam
101 Department of Chronic Disease Prevention
102 Department of Biostatistics and Center for Statistical Genetics
103 SBC - Stockholm Bioinformatics Center
104 Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht
105 INRH
106 Department of Genetics
107 LA BioMed - Los Angeles Biomedical Research Institute
108 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran
109 Western General Hospital
110 Interfaculty Institute for Genetics and Functional Genomics
111 German Research Center for Environmental Health - Helmholtz Center München (GmbH)
112 Medical Research Council
113 Division of Cancer Control and Population Sciences
114 Zhengzhou University of Light Industry
115 Department of Electrical and Electronic Engineering [Niigata Univ.]
116 Genetic Epidemiology Unit
117 Institute of Cardiovascular Science, University College London
118 Aston Business School
119 Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis]
120 CHUV - Centre Hospitalier Universitaire Vaudois
121 Pennington Biomedical Research Center
122 University of Washington [Seattle]
123 Guy's and St Thomas' Hospitals
124 NPU - Northwestern Polytechnical University [Xi'an]
125 Department of Social Medicine
126 Department of Genomics of Common Disease [London, UK]
127 Department of Internal Medicine
128 Institute of Clinical Molecular Biology
129 Medizinische Klinik II
130 Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology
131 Institute for Social Research
132 Division of Statistical Genomics
133 Institute for Clinical Molecular Biology
134 Department of Physics
135 Lund University [Lund]
136 Icelandic Heart Association
137 The Center for Applied Genomics
138 Karolinska Institutet [Stockholm]
139 LGMNPN - Génétique moléculaire de la neurotransmission et des processus neurodégénératifs
140 Medical Research Center Oulu
141 University of Utah School of Medicine [Salt Lake City]
142 The Generation R Study; Pediatrics; Epidemiology
143 CTCN - Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis]
144 Universität Heidelberg [Heidelberg]
145 Interuniversity Cardiology Institute Netherlands
146 National Institute for Health and Welfare [Helsinki]
147 School of Public Health
148 Department of Epidemiology and Public Health
149 Department of Medicine
150 University of Helsinki
151 Institute of Epidemiology and Biobank PopGen
152 Department of Biostatistics, University of Washington
153 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
154 Clinical Institute of Medical and Chemical Laboratory Diagnostics
155 Department of Genetics, Biology and Biochemistry
156 OCDEM - Oxford Centre for Diabetes, Endocrinology and Metabolism
157 QIMR Berghofer Medical Research Institute
158 Department of Genetics
159 Department of Epidemiology
160 UIC - University of Illinois [Chicago]
161 Experimental Cardiology Laboratory
162 Genetic Epidemiology and Clinical Research Group
163 CNR - Consiglio Nazionale delle Ricerche
164 Functional Genomics
165 Department of Epidemiology
166 NHGRI - National Human Genome Research Institute
167 School of Medicine [Los Angeles]
168 Department of Pathological Biochemistry
169 DIfE - German Institute of Human Nutrition Potsdam-Rehbrücke
170 Institute of Metabolic Science
171 University of Maryland School of Medicine [Baltimore, MD, USA]
172 Centre for Molecular Epidemiology
173 Centre for Causal Analyses in Translational Epidemiology
174 IRCCS San Raffaele Scientific Institute [Milan, Italie]
175 U937
Génomique cardiovasculaire
176 BPH - Bordeaux population health
177 Department of Internal Medicine
178 University of Michigan [Ann Arbor]
179 Department of Medical Genetics
180 Singapore Eye Research Institute
181 IETR - Institut d'Électronique et des Technologies du numéRique
182 FIMM - Institute for Molecular Medicine Finland [Helsinki]
183 Department of Psychiatry and Psychotherapy
184 University of Groningen
185 Department of Genomics of Common Disease
186 Department of Microbiology, The Freeman Hospital
187 Department Biostatistics University of North Carolina
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.
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David Clark, Yukinori Okada, Kristjan Moore, Dan Mason, Nicola Pirastu, et al.. Associations of autozygosity with a broad range of human phenotypes. Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.4957. ⟨10.1038/s41467-019-12283-6⟩. ⟨hal-02651737⟩

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