Journal articles

Associations of autozygosity with a broad range of human phenotypes

David J. 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 W 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 J 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 P. 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 I Elliott ⁵⁷ Ralf Ewert Janine Felix Krista Fischer ⁵⁸ Barry I 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 B. 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 K. 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 J. 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 M Starr ¹ Lilja Stefansdottir ^{105, 5} Leon Straker Patrick Sulem ^{50, 5} Gardar Sveinbjornsson ⁵ Morris Swertz ¹⁰⁶ Adele Taylor Kent D 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 U. Völker ¹¹⁰ Eero Vuoksimaa Salma Wakil Melanie Waldenberger ¹¹¹ Gurpreet Wander Ya Xing Wang Nicholas J. 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 I 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 M. van Duijn ¹²⁷ David Ellinghaus ¹²⁸ Jeanette Erdmann ¹²⁹ Johan Eriksson ¹⁷ Evangelos Evangelou ¹³⁰ Michele Evans Jessica Faul ¹³¹ Bjarke Feenstra Mary F. 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 C. 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 L 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 M Martin ¹⁵³ Winfried März ¹⁵⁴ Giuseppe Matullo ¹⁵⁵ Mark I. Mccarthy ¹⁵⁶ Sarah M Medland ¹⁵⁷ Tony Merriman Andres Metspalu ⁴⁴ Brian Meyer Karen L. Mohlke ¹⁵⁸ Grant W. Montgomery ¹¹⁶ Dennis Mook-Kanamori Patricia Munroe Kari E. North ¹⁵⁹ Dale R. Nyholt ¹⁷ Jeffery O’connell Carole C. 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 N Rotimi ¹⁶⁶ Jerome Rotter ¹⁶⁷ Igor Rudan ^{95, 1} Hester den Ruijter Dharambir Sanghera Naveed Sattar ¹⁶⁸ Reinhold Schmidt ⁸⁸ Matthias B Schulze ¹⁶⁹ Heribert Schunkert ¹²⁹ Robert A. Scott ¹⁷⁰ Alan Shuldiner ¹⁷¹ Xueling Sim ¹⁷² Neil Small Jennifer Smith Nona Sotoodehnia E-Shyong Tai Alexander Teumer ⁵⁰ Nicholas J. 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 W. Wright ⁶ Jingyun Yang ⁸⁸ Lei Yu ¹⁸¹ Babette Zemel Alan Zonderman Markus Perola ¹⁸² Patrik K. E. Magnusson ¹⁸³ André Uitterlinden ⁵⁰ Jaspal Kooner Daniel Chasman ⁹⁹ Ruth J. F. Loos ¹⁷⁰ Nora Franceschini ¹⁵⁹ Lude Franke ¹⁸⁴ Chris Haley Caroline Hayward ⁹⁵ Robin G. 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 - Center for Translational Science

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 Helmholtz Zentrum München = German Research Center for Environmental Health

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 [Mexico]

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 UCL - University College of London [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 Helsingin yliopisto = Helsingfors universitet = 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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Santé publique et épidémiologie

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