Hair cortisol in twins : heritability and genetic overlap with psychological variables and stress-system genes
Rietschel, Liz; Streit, Fabian; Zhu, Gu; McAlone, Kerrie; Frank, Josef; Couvy-Duchesne, Baptiste; Witt, Stephanie H.; Binz, Tina M.; McGrath, John; Hickie, Ian B.; Hansel, Narelle K.; Wright, Margaret J.; Gillespie, Nathan A.; Forstner, Andreas J.; Schulze, Thomas G.; Wüst, Stefan; Nöthen, Markus M.; Baumgartner, Markus R.; Walker, Brian R.; Crawford, Andrew A.; Colodro-Conde, Lucía; Medland, Sarah E.; Martin, Nicholas G.; Rietschel, Marcella (2017-11-10)
Rietschel, L., Streit, F., Zhu, G., McAloney, K., … Frank, J. (2017). Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-11852-3
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https://urn.fi/URN:NBN:fi-fe2019062822296
Tiivistelmä
Abstract
Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
Consortia
CORtisolNETwork (CORNET) Consortium
Jennifer L. Bolton21
Caroline Hayward23
Nese Direk24,25
Anna Anderson21
Jennifer Huffman23
James F. Wilson26
Harry Campbell26
Igor Rudan26
Alan Wright23
Nicholas Hastie23
Sarah H. Wild26
Fleur P. Velders24
Albert Hofman24
Andre G. Uitterlinden24,27
Jari Lahti28
Katri Räikkönen28
Eero Kajantie29
Elisabeth Widen30
Aarno Palotie30,31
Johan G. Eriksson29,32,33,34,35
Marika Kaakinen36
Marjo-Riitta Järvelin36,37,38,39
Nicholas J. Timpson40
George Davey Smith40
Susan M. Ring41
David M. Evans40
Beate St Pourcain41
Toshiko Tanaka42
Yuri Milaneschi42,43
Stefania Bandinelli44
Luigi Ferrucci42
Pim van der Harst45,46,47
Judith GM Rosmalen48
Stephen JL Bakker49
Niek Verweij45
Robin PF Dullaart49
Anubha Mahajan50
Cecilia M. Lindgren50
Andrew Morris50
Lars Lind51
Erik Ingelsson51
Laura N. Anderson52
Craig E. Pennell53
Stephen J. Lye52
Stephen G. Matthews54
Joel Eriksson55
Dan Mellstrom55
Claes Ohlsson55
Jackie F. Price26
Mark WJ Strachan21
Rebecca M. Reynolds21
Henning Tiemeier24,56,57
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC)
Stephan Ripke58,59,60
Manuel Mattheisen61,62,63
Abdel Abdellaoui64
Mark J. Adams65
Esben Agerbo66,8,67
Tracy M. Air68
Till FM Andlauer69,70
Silviu-Alin Bacanu71
Marie Bækvad-Hansen67,72
Aartjan TF Beekman43
David A. Bennett73
Klaus Berger74
Tim B. Bigdeli71,11
Jonas Bybjerg-Grauholm67,72
Enda M. Byrne5
Na Cai75
Enrique Castelao76
Toni-Kim Clarke65
Jonathan RI Coleman77
Converge Consortium78
Nick Craddock79
Udo Dannlowski80,81
Gareth Davies82
Gail Davies83
Eco. J. C. de Geus64,84
Philip De Jager85
Ian J. Deary83
Franziska Degenhardt12,13
Erin C. Dunn86,87,88
Erik A. Ehli82
Thalia C. Eley77
Valentina Escott-Price89
Tõnu Esko58,90,91,92
Hilary K. Finucane93,94
Michael Gill95
Scott D. Gordon96
Jakob Grove61,62,67,97
Lynsey S. Hall65,98
Thomas F. Hansen99,100
Christine Søholm Hansen67,72
Thomas F. Hansen101
Andrew C. Heath102
Anjali K. Henders5
Stefan Herms12,13,15
Per Hoffmann12,13,15
Georg Homuth103
Carsten Horn104
Jouke- Jan Hottenga64
David Hougaard67,72
Hailiang Huang59,86,105
Marcus Ising106
Rick Jansen43
Eric Jorgenson107
Stefan Kloiber108,109
James A Knowles110
Warren W. Kretzschmar50
Jesper Krogh111
Zoltán Kutalik112,113
Maren Lang3
Glyn Lewis114
Yihan Li50
Donald J. MacIntyre115,116
Pamela AF Madden102
Jonathan Marchine117
Hamdi Mbarek118,64
Peter McGuffin77
Divya Mehta119
Andres Metspalu92,120
Christel M. Middeldorp64
Evelin Mihailov92,121
Lili Milani92
Grant W. Montgomery122
Sara Mostafavi123,124
Niamh Mullins77
Matthias Nauck125,126
Bernard Ng124
Merete Nordentoft67,127
Dale R. Nyholt128
Michael C. O’Donovan129
Paul F. O’Reilly77
Hogni Oskarsson130
Michael J. Owen129
Sara A. Paciga131
Carsten Bøcker Pedersen66,67,8
Marianne Giørtz Pedersen66,67,8
Nancy L. Pedersen132
Michele L. Pergadia133
Roseann E. Peterson11,71
Erik Pettersson134
Wouter J. Peyrot43
David J. Porteous135
Danielle Posthuma136,137
James B. Potash138
Jorge A. Quiroz139
John P. Rice102
Brien P. Riley71
Margarita Rivera77,140
Douglas M. Ruderfer141
Saira Saeed Mirza24
Robert Schoevers142
Ling Shen107
Jianxin Shi143
Engilbert Sigurdsson144
Grant CB Sinnamon145
Johannes H. Smit43
Daniel J. Smith146
Jordan W. Smoller86
Hreinn Stephansson147
Stacy Steinberg147
Jana Strohmaier3
Katherine E. Tansey148
Alexander Teumer149
Wesley Thompson100,135,150,151,152
Pippa A. Thomson135
Thorgeir E. Thorgeirsson147
Jens Treutlein3
Maciej Trzaskowski153
Daniel Umbricht154
Sandra van der Auwera155
Gerard van Grootheest43
Albert M. van Hemert156
Alexander Viktorin132
Henry Völzke149
Yunpeng Wang67,100,151
Bradley T. Webb157
Myrna M. Weissman158,159
Jürgen Wellmann74
Gonneke Willemsen64
Hualin S. Xi160
Bernhard T. Baune68
Douglas H. R. Blackwood65
Dorret I. Boomsma64
Anders D. Børglum61,62,67
Henriette N. Buttenschøn62,67,161
Sven Cichon12,162,163,164
Enrico Domenici165
Jonathan Flint50,166
Hans J. Grabe155
Steven P. Hamilton167
Kenneth S. Kendler71
Qingqin S. Li168
Susanne Lucae106
Patrik K. Magnusson132
Andrew M. McIntosh65,83
Ole Mors67,169
Preben Bo Mortensen62,8,67
Bertram Müller-Myhsok69,70,170
Brenda WJH Penninx43
Roy H. Perlis87,171
Martin Preisig76
Catherine Schaefer107
Jordan W. Smoller87,88
Kari Stephansson147
Henning Tiemeier24,56,57
Rudolf Uher172
Thomas Werge100,150,173
Ashley R. Winslow174,175
Gerome Breen77,176
Douglas F. Levinson177
Cathryn M. Lewis77,178
Naomi R. Wray5,153
Patrick F. Sullivan134,179,180
23MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
24Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.
25Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, TR, Turkey.
26Centre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH8 9AG, UK.
27Internal Medicine, Erasmus MC, Rotterdam, NL, Netherlands.
28Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
29National Institute for Health and Welfare, Helsinki, Finland.
30Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
31Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
32Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
33Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
34Folkhalsan Research Centre, Helsinki, Finland.
35Vasa Central Hospital, Vasa, Finland.
36Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland.
37Department of Children and Yond People and Families, National Institute for Health and elfare, Oulu, Finland.
38Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London, UK.
39Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
40MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
41School of Social and Community Medicine, University of Bristol, Bristol, UK.
42Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA.
43Department of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, Netherlands.
44Geriatric Unit, ASF, Florence, Italy.
45University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
46University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
47Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Netherlands.
48University of Groningen, University Medical Center Groningen, Interdisciplinary Center for Psychiatric Epidemiology, Groningen, Netherlands.
49University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, Netherlands.
50Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
51Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
52Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
53School of Women’s and Infant’s Health, The University of Western Australia, Crawley, Australia.
54Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
55Center for Bone and Arthritis Research, Institute of Medicin, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
56Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, Netherlands.
57Psychiatry, Erasmus MC, Rotterdam, Netherlands.
58Medical and Population Genetics, Broad Institute, Cambridge, USA.
59Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA.
60Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany.
61Department of Biomedicine, Aarhus University, Aarhus, Denmark.
62iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
63iSPYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
64Dept of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands.
65Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
66Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
67iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
68Discipline of Psychiatry, University of Adelaide, Adelaide, Australia.
69Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
70Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
71Department of Psychiatry, Virginia Commonwealth University, Richmond, USA.
72Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
73Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, USA.
74Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, UK.
75Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK.
76Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland.
77MRC Social Genetic and Developmental Psychiatry Centre, King’s College London, London, UK.
78University of Oxford, Oxford, UK.
79Psychological Medicine, Cardiff University, Cardiff, UK.
80Department of Psychiatry, University of Marburg, Marburg, Germany.
81Department of Psychiatry, University of Münster, Münster, Germany.
82Avera Institute for Human Genetics, Sioux Falls, USA.
83Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
84EMGO+ Institute, VU University Medical Center, Amsterdam, Netherlands.
85Neurology, Brigham and Women’s Hospital, Boston, USA.
86Stanley Center for Psychiatric Research, Broad Institute, Cambridge, USA.
87Department of Psychiatry, Massachusetts General Hospital, Boston, USA.
88Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, USA.
89Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
90Division of Endocrinology, Children’s Hospital Boston, Boston, USA.
91Department of Genetics, Harvard Medical School, Boston, USA.
92Estonian Genome Center, University of Tartu, Tartu, Estonia.
93Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
94Department of Mathematics, Massachusetts Institute of Technology, Cambridge, USA.
95Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
96Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
97Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark.
98Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
99Danish Headache Centre, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark.
100Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Roskilde, Denmark.
101iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark.
102Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, USA.
103Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
104Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
105Department of Medicine, Harvard Medical School, Boston, USA.
106Max Planck Institute of Psychiatry, Munich, Germany.
107Division of Research, Kaiser Permanente Northern California, Oakland, USA.
108Centre for Addiction and Mental Health, Toronto, Canada.
109Department of Psychiatry, University of Toronto, Toronto, Canada.
110Psychiatry & The Behavioral Sciences, University of Southern California, Los Angeles, USA.
111Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark.
112Swiss Institute of Bioinformatics, Lausanne, Switzerland.
113Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
114Division of Psychiatry, University College London, London, UK.
115Mental Health NHS 24, Glasgow, UK.
116Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
117Statistics, University of Oxford, Oxford, UK.
118EMGO+ Institute for Health and Care Research, Amsterdam, Netherlands.
119School of Psychology and Counseling, Queensland University of Technology, Brisbane, Australia.
120Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
121Estonian Biocentre, Tartu, Estonia.
122Institute for Molecular Biology, University of Queensland, Brisbane, Australia.
123Medical Genetics, University of British Columbia, Vancouver, Canada.
124Statistics, University of British Columbia, Vancouver, Canada.
125DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Matthias Nauck, Greifswald, Germany.
126Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
127Mental Health Centre Copenhagen, Copenhagen Universtity Hospital, Copenhagen, Denmark.
128Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
129MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
130Humus, Reykjavik, Iceland.
131Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, USA.
132Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
133Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, USA.
134Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
135Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK.
136Complex Trait Genetics, VU University Amsterdam, Amsterdam, Netherlands.
137Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.
138Psychiatry, University of Iowa, Iowa City, USA.
139Solid GT, Boston, USA.
140Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain.
141Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
142Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
143Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
144Faculty of Medicine, Department of Psychiatry, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
145School of Medicine and Dentistry, James Cook University, Townsville, Australia.
146Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
147deCODE Genetics/Amgen, Reykjavik, Iceland.
148College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
149Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
150iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
151KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
152Department of Psychiatry, University of California, San Diego, San Diego, USA.
153Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
154Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
155Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
156Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands.
157Virginia Institute of Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond, USA.
158Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA.
159Division of Epidemiology, New York State Psychiatric Institute, New York, USA.
160Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, USA.
161Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
162Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
163Department of Biomedicine, University of Basel, Basel, CH, Switzerland.
164Division of Medical Genetics, University of Basel, Basel, CH, Switzerland.
165Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy.
166Psychiatry, University of California Los Angeles, Los Angeles, USA.
167Psychiatry, Kaiser Permanente Northern California, San Francisco, USA.
168Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, USA.
169Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark.
170Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
171Psychiatry, Harvard Medical School, Boston, USA.
172Psychiatry, Dalhousie University, Halifax, Canada.
173Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
174Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Cambridge, USA.
175Orphan Disease Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
176NIHR BRC for Mental Health, King’s College London, London, UK.
177Psychiatry & Behavioral Sciences, Stanford University, Stanford, USA.
178Department of Medical & Molecular Genetics, King’s College London, London, UK.
179Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA.
180Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA.
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