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Nat Commun. 2019 Oct 31;10(1):4957. doi: 10.1038/s41467-019-12283-6.

Associations of autozygosity with a broad range of human phenotypes.

Clark DW1, Okada Y2,3,4, Moore KHS5, Mason D6, Pirastu N1, Gandin I7,8, Mattsson H9,10, Barnes CLK1, Lin K11, Zhao JH12,13, Deelen P14, Rohde R15, Schurmann C16, Guo X17, Giulianini F18, Zhang W19,20, Medina-Gomez C21,22,23, Karlsson R24, Bao Y25, Bartz TM26, Baumbach C27, Biino G28, Bixley MJ29, Brumat M8, Chai JF30, Corre T31,32,33, Cousminer DL34,35, Dekker AM36, Eccles DA37,38, van Eijk KR36, Fuchsberger C39, Gao H19,40, Germain M41,42, Gordon SD43, de Haan HG44, Harris SE45,46, Hofer E47,48, Huerta-Chagoya A49, Igartua C50, Jansen IE51,52, Jia Y17, Kacprowski T53,54, Karlsson T55, Kleber ME56, Li SA57, Li-Gao R44, Mahajan A58, Matsuda K59, Meidtner K60,61, Meng W62, Montasser ME63,64, van der Most PJ65, Munz M66,67,68,69, Nutile T70, Palviainen T71, Prasad G72, Prasad RB73, Priyanka TDS74, Rizzi F75,76, Salvi E76,77, Sapkota BR78, Shriner D79, Skotte L80, Smart MC25, Smith AV81,82, van der Spek A22, Spracklen CN83, Strawbridge RJ84,85, Tajuddin SM86, Trompet S87,88, Turman C89,90, 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Author information

1
Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, Scotland.
2
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
3
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
4
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Osaka, 565-0871, Japan.
5
deCODE genetics/Amgen Inc., Reykjavik 101, Iceland.
6
Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Trust, Bradford, BD96RJ, UK.
7
Research Unit, Area Science Park, Trieste, 34149, Italy.
8
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
9
Unit of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
10
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
11
Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
12
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
13
Cardiovascular Epidemiology Unit, Department of Public health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
14
Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands, Groningen, Groningen, 9700 RB, The Netherlands.
15
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27514, USA.
16
The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, NY, 10029, USA.
17
Division of Genomic Outcomes, Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California, 90502, USA.
18
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
19
Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
20
Department of Cardiology, Ealing Hospital, Middlesex, Middlesex, UB1 3HW, UK.
21
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
22
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
23
The Generation R Study Group, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.
24
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden.
25
Institute for Social and Economic Research, University of Essex, Colchester, CO4 3SQ, UK.
26
Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
27
Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, 85764, Germany.
28
Institute of Molecular Genetics, National Research Council of Italy, Pavia, 27100, Italy.
29
Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
30
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore, 117549, Singapore.
31
Department of Computational Biology, University of Lausanne, Lausanne, 1011, Switzerland.
32
Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
33
Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
34
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
35
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
36
Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.
37
Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia.
38
Malaghan Institute of Medical Research, Wellington, 6242, New Zealand.
39
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, 39100, Italy.
40
MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, UK.
41
INSERM UMR_S 1166, Sorbonne Universités, Paris, 75013, France.
42
ICAN Institute for Cardiometabolism and Nutrition, Paris, 75013, France.
43
QIMR Berghofer Institute of Medical Research, Brisbane, Australia.
44
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
45
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
46
Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
47
Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
48
Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
49
CONACyT, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, 03940, México.
50
Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.
51
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, The Netherlands.
52
Alzheimer Center Department of Neurology, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, 1081HV, The Netherlands.
53
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.
54
Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising-Weihenstephan, 85354, Germany.
55
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75108, Uppsala, Sweden.
56
Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
57
Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Lab for Cancer Research, Frederick, MD, USA.
58
Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
59
Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
60
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
61
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
62
Medical Research Institute, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, UK.
63
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, 21201, USA.
64
Program for Personalized and Genomic Medicine, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, 21201, USA.
65
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
66
Institute for Cardiogenetics, University of Lübeck, Lübeck, 23562, Germany.
67
DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, 23562, Germany.
68
University Heart Center Luebeck, Lübeck, 23562, Germany.
69
Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany.
70
Institute of Genetics and Biophysics A. Buzzati-Traverso - CNR, Naples, 80131, Italy.
71
Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
72
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110020, India.
73
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Skåne University Hospital, Malmö, 20502, Sweden.
74
Genomic Research on Complex diseases (GRC Group), CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, 500007, India.
75
ePhood Scientific Unit, ePhood SRL, Bresso (Milano), 20091, Italy.
76
Department of Health Sciences, University of Milano, Milano, 20139, Italy.
77
Neuroalgology Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milano, 20133, Italy.
78
Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
79
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892-5635, USA.
80
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DK-2300, Denmark.
81
Icelandic Heart Association, Kopavogur, 201, Iceland.
82
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, 101, Iceland.
83
Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
84
Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK.
85
Cardiovascular Medicine Unit, Department of Medicine Solna, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, 171 76, Sweden.
86
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore City, Maryland, 21224, USA.
87
Department of Cardiology, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands.
88
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2300RC, the Netherlands.
89
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
90
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
91
University of Groningen, University Medical Center Groningen, Department of Cardiology, Ther Netherlands, Groningen, 9713 GZ, the Netherlands.
92
Italian Institute for Genomic Medicine (IIGM) and Dept. Medical Sciences, University of Turin, Italy, Turin, 10126, Italy.
93
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110-1093, USA.
94
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
95
Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
96
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 2BN, UK.
97
School of Psychological Science, University of Bristol, Bristol, BS8 1TU, UK.
98
Department of Medicine, GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
99
Department of Genetic Medicine, Weill Cornell Medicine Qatar, Doha, Qatar.
100
Computer and Systems Engineering, Alexandria University, Alexandria, Egypt.
101
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
102
Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, 14080, México.
103
Unidad de Investigacion de Enfermades Metabolicas, Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L., 64710, México.
104
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, 812-8582, Japan.
105
Immunobiology of Dendritic Cells, Institut Pasteur, Paris, 75015, France.
106
Inserm U1223, Paris, 75015, France.
107
Centre for Translational Research, Institut Pasteur, Paris, 75015, France.
108
Department of Cancer Immunology, Genentech Inc, San Francisco, California, 94080, USA.
109
Division of Preventive Medicine, Department of Family Medicine and Public Health, UC San Diego School of Medicine, La Jolla, California, 92093, USA.
110
Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
111
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore, 169856, Singapore.
112
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore, 169857, Singapore.
113
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 119228, SG, Singapore.
114
Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19839-63113, Iran.
115
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
116
Health Science Center at Houston, UTHealth School of Public Health, University of Texas, Houston, TX, 77030, USA.
117
USC-Office of Population Studies Foundation, Inc., Department of Nutrition and Dietetics, Talamban, University of San Carlos, Cebu City, 6000, Cebu, Philippines.
118
Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, University of Utrecht, Utrecht, Utrecht, 3584 CX, Netherlands.
119
Digital Health Center, Hasso Plattner Institute, Universität Potsdam, Potsdam, 14482, Germany.
120
Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
121
Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan, Taiwan.
122
Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, 34137, Italy.
123
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
124
Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
125
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, SG, Singapore.
126
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, 02115, USA.
127
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19839-63113, Iran.
128
Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.
129
MEMO Research, Molecular and Clinical Medicine, University of Dundee, Dundee, DD19SY, UK.
130
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, 17475, Germany.
131
DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, 17475, Germany.
132
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, KSA, 12713, Saudi Arabia.
133
Department of Anthropology, University of Iceland, Reykjavik, 101, Iceland.
134
National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare NHS Trust and Imperial College London, London, UK.
135
UK Dementia Research Institute (UK DRI) at Imperial College London, London, UK.
136
Health Data Research UK - London, London, England.
137
Department of Pediatrics, Erasmus University Medical Center, Rotterdam, 3015CN, The Netherlands.
138
Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, US.
139
Medical Genetics, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
140
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
141
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
142
Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
143
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 101, Iceland.
144
Chinese Academy of Medical Sciences, Beijing, 100730, China.
145
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AF, UK.
146
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, 90089, USA.
147
Blizard Institute, Queen Mary University of London, London, E1 2AT, UK.
148
Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
149
Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, University of Utrecht, Utrecht, Utrecht, 3584 CX, Netherlands.
150
Shanghai Institute of Hematology, State Key Laboratory Of Medical Genomics, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 200025, China.
151
Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan branch, Taipei, Taiwan, Taiwan.
152
School of Medicine, National Defense Medical Center, Taipei, Taiwan, Taiwan.
153
Unit of Public Health Promotion, National Institute for Health and Welfare, Helsinki, Finland.
154
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
155
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
156
Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, 80636, Germany.
157
Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB2 0SR, UK.
158
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore, 138672, Singapore.
159
Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore, 169857.
160
Centre for Global Health, Faculty of Medicine, University of Split, Split, Croatia.
161
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
162
Kuopio University Hospital, Kuopio, Finland.
163
Bristol NIHR Biomedical Research Centre, Bristol, BS8 2BN, UK.
164
Population Health Science, Bristol Medical School, Bristol, BS8 2BY, UK.
165
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan.
166
School of Medicine, National Yang-Ming University, Taipei, Taiwan, Taipei, 112, Taiwan.
167
School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Taichung City, 402, Taiwan.
168
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan.
169
Department of Internal Medicine A, University Medicine Greifswald, Greifswald, 17475, Germany.
170
Department of Epidemiology and Biostatistics, Peking University Health Science Centre, Peking University, Beijing, 100191, China.
171
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore, 138648, Singapore.
172
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 117596, Singapore.
173
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, Durham, NC, 27709, USA.
174
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
175
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
176
Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Università Vita Salute San Raffaele, Milano, 20132, Italy.
177
Helmholtz Zentrum München, Independent Research Group Clinical Epidemiology, Neuherberg, 85764, Germany.
178
Institute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, 85764, Germany.
179
Institute of Human Genetics, Technical University of Munich, Munich, 81675, Germany.
180
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, 80802, Germany.
181
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
182
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
183
Laboratory of Haematology, La Timone Hospital, Marseille, France.
184
INSERM UMR_S 1263, Center for CardioVascular and Nutrition research (C2VN), Aix-Marseille University, Marseille, France.
185
Departamento de Economía, Universidad Autónoma Metropolitana, Mexico, 09340, México.
186
Medical School, The University of Western Australia, Perth, Western Australia/Australia, 6009, Australia.
187
The University of Texas Health Science Center at Houston, School of Public Health, Department of Epidemiology, Human Genetics and Environmental Sciences, Houston, Texas, 77030, USA.
188
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
189
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
190
The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
191
Laboratory of Neurogenetics, Bethesda, MD, 20892, USA.
192
Data Tecnica International LLC, Glen Echo, MD, 20812, USA.
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Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, 17475, Germany.
194
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Headington, Oxford, OX3 7LJ, UK.
195
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
196
Department of Paediatrics, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
197
Instituto Nacional de Medicina Genómica, Mexico, 14610, México.
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Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
199
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
200
Gen-info Ltd, Zagreb, Croatia, Zagreb, Select a Province, 10000, Croatia.
201
International Centre for Circulatory Health, Imperial College London, London, W2 1PG, UK.
202
Imperial Clinical Trials Unit, Imperial College London, London, London, W12 7TA, UK.
203
Human Evolutionary Genetics Unit, Institut Pasteur, Paris, 75015, France.
204
Centre National de la Recherche Scientifique (CNRS) UMR2000, Paris, 75015, France.
205
Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, 75015, France.
206
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, University of Helsinki, Helsinki, 00014, Finland.
207
Hero Heart Institute and Dyanand Medical College and Hospital, Ludhiana, Punjab, India.
208
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.
209
Harvard Medical School, Boston, MA, 02115, USA.
210
Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands.
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Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands.
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IRCCS Neuromed, Pozzilli (IS), 86077, Italy.
213
Gottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Division of Molecular Biology and Biochemistry, Medical University of Graz, 8010, Graz, Austria.
214
Unit of Genomics of Complex Diseases, Institut de Recerca Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
215
San Raffaele Research Institute, Milano, Italy.
216
Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
217
Department of Biostatistics, and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
218
Dept of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, SE-752 37, Uppsala, Sweden.
219
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, Utrecht, 3485 CX, Netherlands.
220
School of Medicine, National Yang-Ming University, Taipei, Taiwan, Taiwan.
221
Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan, Taiwan.
222
School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore, Karnataka, 560078, India.
223
Diabetes Unit, KEM Hospital and Research Centre, Pune, Maharashtra, 411101, India.
224
Symbiosis Statistical Institute, Symbiosis International University, Pune, Maharashtra, 411007, India.
225
Panjab University, Chandigarh, India.
226
Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
227
RCSI Molecular & Cellular Therapeutics (MCT), Royal College of Surgeons in Ireland, RCSI Education & Research Centre, Beaumont Hospital, Dublin 9, Ireland.
228
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, Scotland.
229
School of Physiotherapy and Exercise Science, Faculty of Health Sciences, Curtin University, Perth, Western Australia/Australia, 6102, Australia.
230
Department of Respiratory Medicine, Ghent University Hospital, Ghent, 9000, Belgium.
231
Department of Pathology, University of Vermont, Colchester, VT, 05446, USA.
232
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Mexico, 04510, México.
233
Unidad De Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, 14080, México.
234
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
235
Institute of Genetic and Biomedical Research - Support Unity, National Research Council of Italy, Rome, Italy.
236
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, Scotland.
237
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FI-00014, Finland.
238
Department of Cardiology, Hero DMC Heart Institute, Dayanand Medical College & Hospital, Ludhiana, Punjab, 141001, India.
239
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Lab, Beijing, China, 100005, China.
240
Centre for Population Health Sciences, Usher Institute of Population Health and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, Scotland.
241
Diabetes Unit, K.E.M. Hospital Research Centre, Pune, MAH, 411011, India.
242
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
243
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, Utrecht, 3584 CX, Netherlands.
244
Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, WC1E 6DD, UK.
245
Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands.
246
Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, London, UK.
247
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, 9713GZ, The Netherlands.
248
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
249
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
250
Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.
251
Pennington Biomedical Research Center, Baton Rouge, Louisiane, 70808, USA.
252
Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
253
Quantinuum Research LLC, San Diego, CA, 92101, USA.
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Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
255
Center for Experimental Social Science, Department of Economics, New York University, New York, New York, 10012, USA.
256
Research Institute for Industrial Economics (IFN), Stockholm, 102 15, Sweden.
257
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.
258
Imperial College Healthcare NHS Trust, London, London, W12 0HS, UK.
259
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
260
Institute of Biomedical Technologies Milano, National Research Council of Italy (CNR), Segrate (Milano), 20090, Italy.
261
Bio4Dreams Scientific Unit, Bio4Dreams SRL, Bio4Dreams - business nursery for life sciences, Milano, 20121, Italy.
262
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105, Kiel, Germany.
263
Department of General Practice and Primary health Care, University of Helsinki, Tukholmankatu 8 B, Helsinki, 00014, Finland.
264
National Institute for Health and Welfare, Helsinki, Finland.
265
Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
266
Folkhälsan Research Centre, Helsinki, Finland.
267
Vasa Central Hospital, Vaasa, Finland.
268
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48014, USA.
269
Montreal Heart Institute, Montreal, QC, Canada.
270
Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, Cuernavaca, 01120, México.
271
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
272
Cardiovascular Medicine Unit, Department of Medicine Solna, Centre for Molecular Medicine, Stockholm, 171 76, Sweden.
273
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
274
Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, Singapore.
275
Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, 90014, Finland.
276
Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, 84108, USA.
277
Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 650 West 168th street, PH19-311, Newyork, NY, 10032, USA.
278
Cell Circuits Program, Broad Institute, Cambridge, MA, 02142, USA.
279
Department of Economics, Stockholm School of Economics, Stockholm, SE-113 83, Sweden.
280
Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, 698167, Germany.
281
Department of Public Health, University of Helsinki, Helsinki, FI-00014, Finland.
282
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
283
Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, University of Utrecht, Utrecht, 3584 CX, Netherlands.
284
Helsinki Collegium for Advanced Studies, University of Helsinki, University of Helsinki, Helsinki, 00014, Finland.
285
University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, 24105, Germany.
286
Institute of Epidemiology and PopGen Biobank, University of Kiel, Kiel, Schleswig Holstein, 24105, Germany.
287
Department of Statistics, University of Auckland, Auckland, New Zealand.
288
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
289
Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
290
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
291
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
292
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
293
School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia.
294
Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
295
Department of Medicine, Columbia University Medical Center, New York, New York, USA.
296
Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, The School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
297
School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, New South Wales, Australia.
298
Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia/Australia, 6009, Australia.
299
Department of kinesiology, Laval University, Quebec, QC, G1V 0A6, Canada.
300
Institute of Nutrition and Functional Foods, Laval University, Quebec, QC, G1V 0A6, Canada.
301
Institute of Genetic and Biomedical Research - Support Unity, National Research Council of Italy, Sassari, 07100, Italy.
302
Department of Clinical Genetics, Amsterdam Neuroscience, VU Medical Centre, Amsterdam, 1081HV, The Netherlands.
303
Cardiovascular Health Research Unit, Departments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, 98101, USA.
304
Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
305
Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, H3T 1J4, Canada.
306
Laboratory of Experimental Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, Utrecht, 3584 CX, Netherlands.
307
Oklahoma Center for Neuroscience, Oklahoma City, OK, 73104, USA.
308
Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.
309
Deutsches Zentrum für Herz- und Kreislauferkrankungen (DZHK), Munich Heart Alliance, Munich, 80636, Germany.
310
Regeneron Genetics Center, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591-6607, USA.
311
Faculty of Health Studies, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
312
Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, 98101, USA.
313
Duke-NUS Medical School, National University of Singapore, Singapore, Singapore, 169857, SG, Singapore.
314
Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany.
315
Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2PR, UK.
316
Avon Longitudinal Study of Parents and Children (ALSPAC), University of Bristol, Bristol, BS8 2PR, UK.
317
Endocrinology, Abdominal Centre, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
318
Folkhalsan Research Center, Helsinki, Finland.
319
Research Program of Diabetes and Endocrinology, University of Helsinki, Helsinki, Finland.
320
Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, 1011, Switzerland.
321
Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA.
322
Unit of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, 00271, Finland.
323
National Heart and Lung Institute, Imperial College London, London, W12 0NN, UK.
324
The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
325
Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland.
326
Program in Medical and Population Genetics, Broad Institute, Broad Institute, Cambridge, MASSACHUSETTS, 02142, USA.
327
Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, Scotland. jim.wilson@ed.ac.uk.
328
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, Scotland. jim.wilson@ed.ac.uk.

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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