doi: 10.1016/j.bpsgos.2021.09.001.
eCollection 2022 Oct.
Common Genetic Variation and Age of Onset of Anorexia Nervosa
Hunna J Watson
1
2
3
, Laura M Thornton
1
, Zeynep Yilmaz
1
, Jessica H Baker
1
, Jonathan R I Coleman
4
5
, Roger A H Adan
6
7
8
, Lars Alfredsson
9
, Ole A Andreassen
10
, Helga Ask
11
, Wade H Berrettini
12
, Michael Boehnke
13
, Ilka Boehm
14
, Claudette Boni
15
, Katharina Buehren
16
, Josef Bulant
17
, Roland Burghardt
18
, Xiao Chang
19
, Sven Cichon
20
21
22
23
24
, Roger D Cone
25
, Philippe Courtet
26
, Scott Crow
20
21
22
23
24
, James J Crowley
27
28
, Unna N Danner
29
8
, Martina de Zwaan
30
, George Dedoussis
31
, Janiece E DeSocio
32
, Danielle M Dick
33
34
35
, Dimitris Dikeos
36
, Christian Dina
37
, Srdjan Djurovic
38
39
, Monika Dmitrzak-Weglarz
40
, Elisa Docampo-Martinez
41
42
43
, Philibert Duriez
15
44
, Karin Egberts
45
, Stefan Ehrlich
14
, Johan G Eriksson
46
47
48
, Geòrgia Escaramís
41
42
43
, Tõnu Esko
49
50
, Xavier Estivill
41
42
43
51
, Anne Farmer
4
, Fernando Fernández-Aranda
52
53
, Manfred M Fichter
54
55
, Manuel Föcker
56
, Lenka Foretova
22
, Andreas J Forstner
22
57
58
, Oleksandr Frei
10
59
, Steven Gallinger
60
26
61
, Ina Giegling
62
, Johanna Giuranna
63
, Fragiskos Gonidakis
36
, Philip Gorwood
15
64
, Mònica Gratacòs
41
42
43
, Sébastien Guillaume
60
26
61
, Yiran Guo
19
, Hakon Hakonarson
65
19
, Joanna Hauser
63
66
, Alexandra Havdahl
67
11
63
, Johannes Hebebrand
63
66
, Sietske G Helder
4
68
, Stefan Herms
23
24
, Beate Herpertz-Dahlmann
16
, Wolfgang Herzog
69
, Anke Hinney
67
11
63
, Christopher Hübel
5
, James I Hudson
70
, Hartmut Imgart
71
, Stephanie Jamain
72
, Vladimir Janout
73
, Susana Jiménez-Murcia
52
53
, Ian R Jones
74
, Antonio Julià
75
, Gursharan Kalsi
4
, Deborah Kaminská
76
, Jaakko Kaprio
77
, Leila Karhunen
78
79
, Martien J H Kas
7
80
, Pamela K Keel
81
, James L Kennedy
82
83
84
, Anna Keski-Rahkonen
85
, Kirsty Kiezebrink
86
, Lars Klareskog
78
79
, Kelly L Klump
87
, Gun Peggy S Knudsen
11
, Maria C La Via
1
, Stephanie Le Hellard
88
89
90
, Marion Leboyer
91
92
72
, Dong Li
19
, Lisa Lilenfeld
93
, Bochao Lin
7
, Jolanta Lissowska
7
94
, Jurjen Luykx
7
94
, Pierre Magistretti
95
96
97
, Mario Maj
10
98
, Sara Marsal
99
100
75
, Christian R Marshall
101
, Morten Mattingsdal
10
98
, Ingrid Meulenbelt
102
, Nadia Micali
103
104
, Karen S Mitchell
105
106
, Alessio Maria Monteleone
98
, Palmiero Monteleone
95
96
97
, Richard Myers
107
, Marie Navratilova
108
, Ionna Ntalla
31
, Julie K O'Toole
109
, Roel A Ophoff
110
111
, Leonid Padyukov
78
, Jacques Pantel
112
, Hana Papežová
113
, Dalila Pinto
114
, Anu Raevuori
115
85
116
117
, Nicolas Ramoz
15
, Ted Reichborn-Kjennerud
118
11
, Valdo Ricca
119
120
, Samuli Ripatti
49
121
122
123
77
124
125
, Stephan Ripke
49
121
122
123
77
124
125
, Franziska Ritschel
14
126
127
, Marion Roberts
4
, Alessandro Rotondo
85
116
117
, Dan Rujescu
62
, Filip Rybakowski
14
126
127
, André Scherag
128
129
, Stephen W Scherer
130
131
, Ulrike Schmidt
132
5
, Laura J Scott
13
, Jochen Seitz
16
, Yasmina Silén
85
, Lenka Šlachtová
133
, P Eline Slagboom
102
, Margarita C T Slof-Op 't Landt
134
135
, Agnieszka Slopien
128
129
, Sandro Sorbi
119
136
, Beata Świątkowska
137
, Alfonso Tortorella
138
139
, Federica Tozzi
140
, Janet Treasure
132
5
, Artemis Tsitsika
138
139
, Marta Tyszkiewicz-Nwafor
129
, Konstantinos Tziouvas
141
, Annemarie A van Elburg
29
8
, Eric F van Furth
134
135
, Esther Walton
14
142
, Elisabeth Widen
14
142
, Stephanie Zerwas
1
143
144
, Stephan Zipfel
1
143
144
, Andrew W Bergen
145
146
, Joseph M Boden
147
, Harry Brandt
21
, Steven Crawford
20
21
22
23
24
, Katherine A Halmi
148
, L John Horwood
147
, Craig Johnson
149
, Allan S Kaplan
82
83
84
, Walter H Kaye
150
, James E Mitchell
151
, Catherine M Olsen
152
, John F Pearson
153
, Nancy L Pedersen
91
, Michael Strober
154
155
, Thomas Werge
156
, David C Whiteman
60
, D Blake Woodside
82
83
157
158
, Scott Gordon
60
26
61
, Sarah Maguire
99
100
75
, Janne T Larsen
159
160
161
, Richard Parker
60
, Liselotte V Petersen
159
160
161
, Jennifer Jordan
147
162
, Martin Kennedy
163
, Tracey D Wade
164
, Andreas Birgegård
91
, Paul Lichtenstein
91
, Mikael Landén
91
92
72
, Nicholas G Martin
60
, Preben Bo Mortensen
159
160
161
, Gerome Breen
4
5
, Cynthia M Bulik
1
165
91
Affiliations
Affiliations
- 1 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- 2 School of Psychology, Curtin University, Perth, Western Australia, Australia.
- 3 Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.
- 4 Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
- 5 National Institute for Health Research Biomedical Research Centre, King's College London and South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
- 6 Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- 7 Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, the Netherlands.
- 8 Altrecht Eating Disorders Rintveld, Zeist, the Netherlands.
- 9 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
- 10 NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
- 11 Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
- 12 Department of Psychiatry, Center for Neurobiology and Behavior, Philadelphia, Pennsylvania.
- 13 Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
- 14 Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
- 15 INSERM 1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
- 16 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.
- 17 Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 18 Department of Child and Adolescent Psychiatry, Klinikum Frankfurt/Oder, Frankfurt, Germany.
- 19 Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
- 20 Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
- 21 The Center for Eating Disorders at Sheppard Pratt, Baltimore, Maryland.
- 22 Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.
- 23 Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
- 24 Department of Biomedicine, University of Basel, Basel, Switzerland.
- 25 Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
- 26 Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France.
- 27 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- 28 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
- 29 Department of Clinical Psychology, Faculty of Social Sciences, University Utrecht, Utrecht, the Netherlands.
- 30 Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany.
- 31 Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
- 32 College of Nursing, Seattle University, Seattle, Washington.
- 33 Department of Psychology, Commonwealth University, Richmond, Virginia.
- 34 College Behavioral and Emotional Health Institute, Commonwealth University, Richmond, Virginia.
- 35 Department of Human and Molecular Genetics, Commonwealth University, Richmond, Virginia.
- 36 First Department of Psychiatry, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece.
- 37 L'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
- 38 NORMENT Centre, Department of Clinical Science, University of Oslo, Oslo, Norway.
- 39 Department of Medical Genetics, University of Bergen, Bergen, Norway.
- 40 Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
- 41 Barcelona Institute of Science and Technology, Barcelona, Spain.
- 42 Universitat Pompeu Fabra, Barcelona, Spain.
- 43 Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.
- 44 GHU Paris Psychiatrie et Neurosciences, CMME, Paris, France.
- 45 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany.
- 46 Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
- 47 Folkhälsan Research Center, Helsinki, Finland.
- 48 Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- 49 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
- 50 Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
- 51 Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain.
- 52 Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, Spain.
- 53 Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain.
- 54 Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
- 55 Schön Klinik Roseneck Affiliated With the Medical Faculty of the University of Munich, Prien, Germany.
- 56 Department of Child and Adolescent Psychiatry, University Hospital Münster, Münster, Germany.
- 57 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
- 58 Centre for Human Genetics, University of Marburg, Marburg, Germany.
- 59 NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 60 QIMR Berghofer Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
- 61 Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
- 62 Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
- 63 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
- 64 CMME (GHU Paris Psychiatrie et Neurosciences), Hôpital Sainte Anne, Paris, France.
- 65 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
- 66 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 67 Nic Waals Institute, Lovisenberg Diaconal Hospitaland, Oslo, Norway.
- 68 Zorg op Orde, Delft, the Netherlands.
- 69 Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
- 70 Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, Massachusetts.
- 71 Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany.
- 72 Inserm U955, Institut Mondor de recherches Biomédicales, Laboratoire, Neuro-Psychiatrie Translationnelle, and Fédération Hospitalo-Universitaire de Précision Médecine en Addictologie et Psychiatrie, University Paris-Est-Créteil, Créteil, France.
- 73 Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
- 74 National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
- 75 Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
- 76 Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 77 Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
- 78 Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.
- 79 Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
- 80 Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
- 81 Department of Psychology, Florida State University, Tallahassee, Florida.
- 82 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
- 83 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- 84 Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
- 85 Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.
- 86 Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
- 87 Department of Psychology, Michigan State University, Lansing, Michigan.
- 88 Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research, University of Bergen, Bergen, Norway.
- 89 Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
- 90 Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway.
- 91 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- 92 Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden.
- 93 Department of Clinical Psychology, the Chicago School of Professional Psychology, Washington, DC.
- 94 Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
- 95 Department of Psychiatry, University of Lausanne-University Hospital of Lausanne, Lausanne, Switzerland.
- 96 BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
- 97 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
- 98 Department of Psychiatry, University of Campania "Luigi Vanvitelli," Naples, Italy.
- 99 InsideOut Institute for Eating Disorders, The Charles Perkins Centre, the University of Sydney, Sydney, New South Wales, Australia.
- 100 Sydney Local Health District, NSW Health, St. Leonards, New South Wales, Australia.
- 101 Department of Paediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada.
- 102 Department of Biomedical Data Science, Leiden University Medical Centre, Leiden, the Netherlands.
- 103 Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
- 104 Department of Pediatrics Gynaecology and Obstetrics, University of Geneva, Geneva, Switzerland.
- 105 Women's Health Sciences Division, National Center for PTSD, Boston, Massachusetts.
- 106 Department of Psychiatry, Boston University, Boston, Massachusetts.
- 107 HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
- 108 Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
- 109 Kartini Clinic, Portland, Oregon.
- 110 Center for Neurobehavioral Genetics, University of California at Los Angeles, Los Angeles, California.
- 111 Department of Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
- 112 INSERM 1124, Université de Paris, Paris, France.
- 113 Eating Disorders Unit, Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 114 Division of Psychiatric Genomics, Department of Psychiatry, and Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York.
- 115 Department of Adolescent Psychiatry, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
- 116 Department of Adolescent Psychiatry, University of Helsinki, Helsinki, Finland.
- 117 Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy.
- 118 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 119 Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
- 120 Department of Health Science, University of Florence, Florence, Italy.
- 121 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
- 122 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
- 123 Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
- 124 Department of Public Health, University of Helsinki, Helsinki, Finland.
- 125 Department of Biometry, University of Helsinki, Helsinki, Finland.
- 126 Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
- 127 Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 128 Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
- 129 Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 130 McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
- 131 Department of Genetics and Genome Biology and the Center for Applied Genomics, the Hospital for Sick Children, Toronto, Ontario, Canada.
- 132 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
- 133 Department of Biochemistry and Molecular Biology, Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic.
- 134 Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands.
- 135 Rivierduinen Eating Disorders Ursula, Leiden, the Netherlands.
- 136 IRCSS Fondazione Don Carlo Gnocchi, Florence, Italy.
- 137 Department of Environmental Epidemiology, the Reference Center for Asbestos Exposure and Health Risk Assessment, Lódź, Poland.
- 138 Adolescent Health Unit, Second Department of Pediatrics, Athens, Greece.
- 139 Department of Psychiatry, University of Perugia, Perugia, Italy.
- 140 Brain Sciences Department, Stremble Ventures, Limassol, Cyprus.
- 141 Pediatric Intensive Care Unit, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
- 142 Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, Helsinki, Finland.
- 143 Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany.
- 144 Centre of Excellence for Eating Disorders, University Tuebingen, Tuebingen, Germany.
- 145 Oregon Research Institute, Eugene, Oregon.
- 146 Biorealm Research, Walnut, California.
- 147 Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
- 148 New York Presbyterian Hospital-Westchester Division, Weill Cornell Medical College of Cornell University, White Plains, New York.
- 149 Eating Recovery Center, Denver, Colorado.
- 150 Department of Psychiatry, University of California San Diego, San Diego, California.
- 151 Department of Psychiatry and Behavioral Science, School of Medicine and Health Sciences, University of North Dakota, Fargo, North Dakota.
- 152 Cancer Control Group, University of Queensland, Brisbane, Queensland, Australia.
- 153 Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand.
- 154 Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California.
- 155 David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
- 156 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
- 157 Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
- 158 Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada.
- 159 National Centre for Register-based Research, Aarhus BSS, Aarhus, Denmark.
- 160 Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.
- 161 Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
- 162 Clinical Research Unit, Canterbury District Health Board, Christchurch, New Zealand.
- 163 Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
- 164 College of Education, Psychology and Social Work, Flinders University, Adelaide, South Australia, Australia.
- 165 Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- PMID: 36324647
- PMCID: PMC9616394
- DOI: 10.1016/j.bpsgos.2021.09.001
Item in Clipboard
Common Genetic Variation and Age of Onset of Anorexia Nervosa
Hunna J Watson et al.
Biol Psychiatry Glob Open Sci.
.
Display options
Format
doi: 10.1016/j.bpsgos.2021.09.001.
eCollection 2022 Oct.
Authors
Hunna J Watson
1
2
3
, Laura M Thornton
1
, Zeynep Yilmaz
1
, Jessica H Baker
1
, Jonathan R I Coleman
4
5
, Roger A H Adan
6
7
8
, Lars Alfredsson
9
, Ole A Andreassen
10
, Helga Ask
11
, Wade H Berrettini
12
, Michael Boehnke
13
, Ilka Boehm
14
, Claudette Boni
15
, Katharina Buehren
16
, Josef Bulant
17
, Roland Burghardt
18
, Xiao Chang
19
, Sven Cichon
20
21
22
23
24
, Roger D Cone
25
, Philippe Courtet
26
, Scott Crow
20
21
22
23
24
, James J Crowley
27
28
, Unna N Danner
29
8
, Martina de Zwaan
30
, George Dedoussis
31
, Janiece E DeSocio
32
, Danielle M Dick
33
34
35
, Dimitris Dikeos
36
, Christian Dina
37
, Srdjan Djurovic
38
39
, Monika Dmitrzak-Weglarz
40
, Elisa Docampo-Martinez
41
42
43
, Philibert Duriez
15
44
, Karin Egberts
45
, Stefan Ehrlich
14
, Johan G Eriksson
46
47
48
, Geòrgia Escaramís
41
42
43
, Tõnu Esko
49
50
, Xavier Estivill
41
42
43
51
, Anne Farmer
4
, Fernando Fernández-Aranda
52
53
, Manfred M Fichter
54
55
, Manuel Föcker
56
, Lenka Foretova
22
, Andreas J Forstner
22
57
58
, Oleksandr Frei
10
59
, Steven Gallinger
60
26
61
, Ina Giegling
62
, Johanna Giuranna
63
, Fragiskos Gonidakis
36
, Philip Gorwood
15
64
, Mònica Gratacòs
41
42
43
, Sébastien Guillaume
60
26
61
, Yiran Guo
19
, Hakon Hakonarson
65
19
, Joanna Hauser
63
66
, Alexandra Havdahl
67
11
63
, Johannes Hebebrand
63
66
, Sietske G Helder
4
68
, Stefan Herms
23
24
, Beate Herpertz-Dahlmann
16
, Wolfgang Herzog
69
, Anke Hinney
67
11
63
, Christopher Hübel
5
, James I Hudson
70
, Hartmut Imgart
71
, Stephanie Jamain
72
, Vladimir Janout
73
, Susana Jiménez-Murcia
52
53
, Ian R Jones
74
, Antonio Julià
75
, Gursharan Kalsi
4
, Deborah Kaminská
76
, Jaakko Kaprio
77
, Leila Karhunen
78
79
, Martien J H Kas
7
80
, Pamela K Keel
81
, James L Kennedy
82
83
84
, Anna Keski-Rahkonen
85
, Kirsty Kiezebrink
86
, Lars Klareskog
78
79
, Kelly L Klump
87
, Gun Peggy S Knudsen
11
, Maria C La Via
1
, Stephanie Le Hellard
88
89
90
, Marion Leboyer
91
92
72
, Dong Li
19
, Lisa Lilenfeld
93
, Bochao Lin
7
, Jolanta Lissowska
7
94
, Jurjen Luykx
7
94
, Pierre Magistretti
95
96
97
, Mario Maj
10
98
, Sara Marsal
99
100
75
, Christian R Marshall
101
, Morten Mattingsdal
10
98
, Ingrid Meulenbelt
102
, Nadia Micali
103
104
, Karen S Mitchell
105
106
, Alessio Maria Monteleone
98
, Palmiero Monteleone
95
96
97
, Richard Myers
107
, Marie Navratilova
108
, Ionna Ntalla
31
, Julie K O'Toole
109
, Roel A Ophoff
110
111
, Leonid Padyukov
78
, Jacques Pantel
112
, Hana Papežová
113
, Dalila Pinto
114
, Anu Raevuori
115
85
116
117
, Nicolas Ramoz
15
, Ted Reichborn-Kjennerud
118
11
, Valdo Ricca
119
120
, Samuli Ripatti
49
121
122
123
77
124
125
, Stephan Ripke
49
121
122
123
77
124
125
, Franziska Ritschel
14
126
127
, Marion Roberts
4
, Alessandro Rotondo
85
116
117
, Dan Rujescu
62
, Filip Rybakowski
14
126
127
, André Scherag
128
129
, Stephen W Scherer
130
131
, Ulrike Schmidt
132
5
, Laura J Scott
13
, Jochen Seitz
16
, Yasmina Silén
85
, Lenka Šlachtová
133
, P Eline Slagboom
102
, Margarita C T Slof-Op 't Landt
134
135
, Agnieszka Slopien
128
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, Sandro Sorbi
119
136
, Beata Świątkowska
137
, Alfonso Tortorella
138
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, Federica Tozzi
140
, Janet Treasure
132
5
, Artemis Tsitsika
138
139
, Marta Tyszkiewicz-Nwafor
129
, Konstantinos Tziouvas
141
, Annemarie A van Elburg
29
8
, Eric F van Furth
134
135
, Esther Walton
14
142
, Elisabeth Widen
14
142
, Stephanie Zerwas
1
143
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, Stephan Zipfel
1
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, Andrew W Bergen
145
146
, Joseph M Boden
147
, Harry Brandt
21
, Steven Crawford
20
21
22
23
24
, Katherine A Halmi
148
, L John Horwood
147
, Craig Johnson
149
, Allan S Kaplan
82
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, Walter H Kaye
150
, James E Mitchell
151
, Catherine M Olsen
152
, John F Pearson
153
, Nancy L Pedersen
91
, Michael Strober
154
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, Thomas Werge
156
, David C Whiteman
60
, D Blake Woodside
82
83
157
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, Scott Gordon
60
26
61
, Sarah Maguire
99
100
75
, Janne T Larsen
159
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, Richard Parker
60
, Liselotte V Petersen
159
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, Jennifer Jordan
147
162
, Martin Kennedy
163
, Tracey D Wade
164
, Andreas Birgegård
91
, Paul Lichtenstein
91
, Mikael Landén
91
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, Nicholas G Martin
60
, Preben Bo Mortensen
159
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, Gerome Breen
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, Cynthia M Bulik
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Affiliations
- 1 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- 2 School of Psychology, Curtin University, Perth, Western Australia, Australia.
- 3 Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.
- 4 Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
- 5 National Institute for Health Research Biomedical Research Centre, King's College London and South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
- 6 Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- 7 Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, the Netherlands.
- 8 Altrecht Eating Disorders Rintveld, Zeist, the Netherlands.
- 9 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
- 10 NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
- 11 Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
- 12 Department of Psychiatry, Center for Neurobiology and Behavior, Philadelphia, Pennsylvania.
- 13 Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
- 14 Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
- 15 INSERM 1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
- 16 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.
- 17 Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 18 Department of Child and Adolescent Psychiatry, Klinikum Frankfurt/Oder, Frankfurt, Germany.
- 19 Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
- 20 Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
- 21 The Center for Eating Disorders at Sheppard Pratt, Baltimore, Maryland.
- 22 Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.
- 23 Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
- 24 Department of Biomedicine, University of Basel, Basel, Switzerland.
- 25 Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
- 26 Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France.
- 27 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- 28 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
- 29 Department of Clinical Psychology, Faculty of Social Sciences, University Utrecht, Utrecht, the Netherlands.
- 30 Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany.
- 31 Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
- 32 College of Nursing, Seattle University, Seattle, Washington.
- 33 Department of Psychology, Commonwealth University, Richmond, Virginia.
- 34 College Behavioral and Emotional Health Institute, Commonwealth University, Richmond, Virginia.
- 35 Department of Human and Molecular Genetics, Commonwealth University, Richmond, Virginia.
- 36 First Department of Psychiatry, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece.
- 37 L'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
- 38 NORMENT Centre, Department of Clinical Science, University of Oslo, Oslo, Norway.
- 39 Department of Medical Genetics, University of Bergen, Bergen, Norway.
- 40 Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
- 41 Barcelona Institute of Science and Technology, Barcelona, Spain.
- 42 Universitat Pompeu Fabra, Barcelona, Spain.
- 43 Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain.
- 44 GHU Paris Psychiatrie et Neurosciences, CMME, Paris, France.
- 45 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany.
- 46 Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
- 47 Folkhälsan Research Center, Helsinki, Finland.
- 48 Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- 49 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
- 50 Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
- 51 Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain.
- 52 Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, Spain.
- 53 Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain.
- 54 Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
- 55 Schön Klinik Roseneck Affiliated With the Medical Faculty of the University of Munich, Prien, Germany.
- 56 Department of Child and Adolescent Psychiatry, University Hospital Münster, Münster, Germany.
- 57 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
- 58 Centre for Human Genetics, University of Marburg, Marburg, Germany.
- 59 NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 60 QIMR Berghofer Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
- 61 Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
- 62 Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
- 63 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
- 64 CMME (GHU Paris Psychiatrie et Neurosciences), Hôpital Sainte Anne, Paris, France.
- 65 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
- 66 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 67 Nic Waals Institute, Lovisenberg Diaconal Hospitaland, Oslo, Norway.
- 68 Zorg op Orde, Delft, the Netherlands.
- 69 Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
- 70 Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, Massachusetts.
- 71 Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany.
- 72 Inserm U955, Institut Mondor de recherches Biomédicales, Laboratoire, Neuro-Psychiatrie Translationnelle, and Fédération Hospitalo-Universitaire de Précision Médecine en Addictologie et Psychiatrie, University Paris-Est-Créteil, Créteil, France.
- 73 Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
- 74 National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
- 75 Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
- 76 Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 77 Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
- 78 Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.
- 79 Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
- 80 Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
- 81 Department of Psychology, Florida State University, Tallahassee, Florida.
- 82 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
- 83 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- 84 Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
- 85 Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.
- 86 Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
- 87 Department of Psychology, Michigan State University, Lansing, Michigan.
- 88 Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research, University of Bergen, Bergen, Norway.
- 89 Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
- 90 Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway.
- 91 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- 92 Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden.
- 93 Department of Clinical Psychology, the Chicago School of Professional Psychology, Washington, DC.
- 94 Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
- 95 Department of Psychiatry, University of Lausanne-University Hospital of Lausanne, Lausanne, Switzerland.
- 96 BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
- 97 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
- 98 Department of Psychiatry, University of Campania "Luigi Vanvitelli," Naples, Italy.
- 99 InsideOut Institute for Eating Disorders, The Charles Perkins Centre, the University of Sydney, Sydney, New South Wales, Australia.
- 100 Sydney Local Health District, NSW Health, St. Leonards, New South Wales, Australia.
- 101 Department of Paediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada.
- 102 Department of Biomedical Data Science, Leiden University Medical Centre, Leiden, the Netherlands.
- 103 Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
- 104 Department of Pediatrics Gynaecology and Obstetrics, University of Geneva, Geneva, Switzerland.
- 105 Women's Health Sciences Division, National Center for PTSD, Boston, Massachusetts.
- 106 Department of Psychiatry, Boston University, Boston, Massachusetts.
- 107 HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
- 108 Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
- 109 Kartini Clinic, Portland, Oregon.
- 110 Center for Neurobehavioral Genetics, University of California at Los Angeles, Los Angeles, California.
- 111 Department of Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
- 112 INSERM 1124, Université de Paris, Paris, France.
- 113 Eating Disorders Unit, Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
- 114 Division of Psychiatric Genomics, Department of Psychiatry, and Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York.
- 115 Department of Adolescent Psychiatry, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
- 116 Department of Adolescent Psychiatry, University of Helsinki, Helsinki, Finland.
- 117 Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy.
- 118 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 119 Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
- 120 Department of Health Science, University of Florence, Florence, Italy.
- 121 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
- 122 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
- 123 Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
- 124 Department of Public Health, University of Helsinki, Helsinki, Finland.
- 125 Department of Biometry, University of Helsinki, Helsinki, Finland.
- 126 Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
- 127 Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 128 Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
- 129 Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 130 McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
- 131 Department of Genetics and Genome Biology and the Center for Applied Genomics, the Hospital for Sick Children, Toronto, Ontario, Canada.
- 132 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
- 133 Department of Biochemistry and Molecular Biology, Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic.
- 134 Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands.
- 135 Rivierduinen Eating Disorders Ursula, Leiden, the Netherlands.
- 136 IRCSS Fondazione Don Carlo Gnocchi, Florence, Italy.
- 137 Department of Environmental Epidemiology, the Reference Center for Asbestos Exposure and Health Risk Assessment, Lódź, Poland.
- 138 Adolescent Health Unit, Second Department of Pediatrics, Athens, Greece.
- 139 Department of Psychiatry, University of Perugia, Perugia, Italy.
- 140 Brain Sciences Department, Stremble Ventures, Limassol, Cyprus.
- 141 Pediatric Intensive Care Unit, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.
- 142 Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, Helsinki, Finland.
- 143 Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tuebingen, Tuebingen, Germany.
- 144 Centre of Excellence for Eating Disorders, University Tuebingen, Tuebingen, Germany.
- 145 Oregon Research Institute, Eugene, Oregon.
- 146 Biorealm Research, Walnut, California.
- 147 Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
- 148 New York Presbyterian Hospital-Westchester Division, Weill Cornell Medical College of Cornell University, White Plains, New York.
- 149 Eating Recovery Center, Denver, Colorado.
- 150 Department of Psychiatry, University of California San Diego, San Diego, California.
- 151 Department of Psychiatry and Behavioral Science, School of Medicine and Health Sciences, University of North Dakota, Fargo, North Dakota.
- 152 Cancer Control Group, University of Queensland, Brisbane, Queensland, Australia.
- 153 Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand.
- 154 Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California.
- 155 David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
- 156 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
- 157 Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
- 158 Program for Eating Disorders, University Health Network, Toronto, Ontario, Canada.
- 159 National Centre for Register-based Research, Aarhus BSS, Aarhus, Denmark.
- 160 Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.
- 161 Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
- 162 Clinical Research Unit, Canterbury District Health Board, Christchurch, New Zealand.
- 163 Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
- 164 College of Education, Psychology and Social Work, Flinders University, Adelaide, South Australia, Australia.
- 165 Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
- PMID: 36324647
- PMCID: PMC9616394
- DOI: 10.1016/j.bpsgos.2021.09.001
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Abstract
Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.
Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.
Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h 2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN.
Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
Keywords: Age of onset; Anorexia nervosa; Early-onset; GWAS; Genetic risk score; Genetics; Menarche; Mendelian randomization; Puberty.
© 2021 The Authors.
Figures
Figure 1
Early-onset and typical-onset AN show…
Figure 1
Early-onset and typical-onset AN show significantly different genetic correlation patterns with risk and…
Early-onset and typical-onset AN show significantly different genetic correlation patterns with risk and comorbid traits. FDR-significant differences in genetic correlations were detected in two categories—anthropometric and reproductive—within six previously identified categories of risk or comorbid traits of interest for AN. (A) Sixty-two phenotypes were tested; duplicate phenotypes are not plotted (for duplicate phenotypes, we prioritized published summary statistics or the rg difference with the lowest SE). Full results are shown in Table S9 in Supplement 2. (B) Shows the rgs between the phenotypes and the age of onset subphenotypes. The error bars in both plots represent the SE. ADHD, attention-deficit/hyperactivity disorder; AN, anorexia nervosa; BMI, body mass index; FDR, false discovery rate; HbA1C, hemoglobin A1c; HDL, high-density lipoprotein; HOMA-B, homeostatic model assessment for beta cell function; HOMA-IR, HOMA for insulin resistance; LDL, low-density lipoprotein; PGC, Psychiatric Genomics Consortium; RGC, ReproGen Consortium; UKB, UK Biobank.
Figure 2
GRS age of onset and…
Figure 2
GRS age of onset and GRS early-onset AN significantly predict age of onset…
GRSage of onset and GRSearly-onset AN significantly predict age of onset of AN. The p values are false discovery rate–corrected for multiple testing. ∗p < .05; ∗∗∗p < .001. (A) Unstandardized βs represent the average increase in age of onset (years) per 1-unit increase in GRS. The error bars are 95% confidence intervals. The eight data points in each field, from left to right, represent ascending p value selection thresholds (pT < .001, pT < .01, pT < .1, pT < .2, pT < .3, pT < .4, pT < .5, pT < 1) for inclusion of SNPs from the GWAS into the GRS (i.e., pT < 1 means that all SNPs were included in score calculation). Table S10 in Supplement 2 reports descriptive statistics for GRS. (B) Marginal means and standard errors are plotted. The tests of significant difference are from fixed-effects inverse-variance weighted meta-analyses of mean difference in age of onset by GRS quartile. The data include 13 cohorts (n = 9335) for GRSage of onset and GRSAN and 5 cohorts (n = 8267) for GRSearly-onset AN. AN, anorexia nervosa; GRS, genetic risk score; GRSAAO, GRS computed from the within-case age of onset GWAS; GRSAN, GRS computed from the case-control AN GWAS (2); GRSearly−onset AN, GRS computed from the case-control early-onset AN GWAS; GWAS, genome-wide association study; SNP, single nucleotide polymorphism.
References
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- Zipfel S., Giel K.E., Bulik C.M., Hay P., Schmidt U. Anorexia nervosa: Aetiology, assessment, and treatment. Lancet Psychiatry. 2015;2:1099–1111. - PubMed
