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Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression

View ORCID ProfileSP Hagenaars, JRI Coleman, S Choi, H Gaspar, MJ Adams, D Howard, K Hodgson, M Traylor, TM Air, TFM Andlauer, V Arolt, BT Baune, EB Binder, DHR Blackwood, DI Boomsma, A Campbell, M Cearns, D Czamara, U Dannlowski, K Domschke, EJC de Geus, SP Hamilton, C Hayward, I Hickie, JJ Hottenga, M Ising, I Jones, LA Jones, Z Kutalik, S Lucae, NG Martin, Y Milaneschi, B Mueller-Myhsok, MJ Owen, S Padmanabhan, BWJH Penninx, G Pistis, DJ Porteous, M Preisig, S Ripke, SI Shyn, PF Sullivan, J Whitfield, NR Wray, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, MEGASTROKE consortium, AM McIntosh, IJ Deary, G Breen, CM Lewis
doi: https://doi.org/10.1101/645077
SP Hagenaars
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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  • ORCID record for SP Hagenaars
  • For correspondence: saskia.hagenaars@kcl.ac.uk
JRI Coleman
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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S Choi
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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H Gaspar
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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MJ Adams
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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D Howard
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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K Hodgson
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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M Traylor
4Stroke Research Group, Division of Clinical Neurosciences, University of Cambridge, UK
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TM Air
5Discipline of Psychiatry, University of Adelaide, Adelaide, SA, AU
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TFM Andlauer
6Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, DE
7Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, DE
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V Arolt
8Department of Psychiatry, University of Münster, Münster, Nordrhein-Westfalen, DE
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BT Baune
8Department of Psychiatry, University of Münster, Münster, Nordrhein-Westfalen, DE
9Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, AU
10Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, AU
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EB Binder
11Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, DE
12Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, US
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DHR Blackwood
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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DI Boomsma
13Dept of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, NL
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A Campbell
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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M Cearns
9Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, AU
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D Czamara
14Max Planck Institute of Psychiatry, Munich, DE
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U Dannlowski
8Department of Psychiatry, University of Münster, Münster, Nordrhein-Westfalen, DE
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K Domschke
15Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, DE
16Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, DE
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EJC de Geus
13Dept of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, NL
17Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, NL
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SP Hamilton
18Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, US
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C Hayward
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
30MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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I Hickie
19Brain and Mind Centre, University of Sydney, Sydney, NSW, AU
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JJ Hottenga
13Dept of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, NL
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M Ising
14Max Planck Institute of Psychiatry, Munich, DE
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I Jones
20MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, GB
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LA Jones
21Department of Psychological Medicine, University of Worcester, Worcester, GB
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Z Kutalik
22Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, VD, CH
23Swiss Institute of Bioinformatics, Lausanne, VD, CH
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S Lucae
14Max Planck Institute of Psychiatry, Munich, DE
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NG Martin
24Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, AU
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Y Milaneschi
25Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, NL
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B Mueller-Myhsok
6Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, DE
26Munich Cluster for Systems Neurology (SyNergy), Munich, DE
27University of Liverpool, Liverpool, GB
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MJ Owen
20MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, GB
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S Padmanabhan
28Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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BWJH Penninx
25Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, NL
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G Pistis
31Department of Psychiatry, University Hospital of Lausanne, Prilly, Vaud, CH
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DJ Porteous
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
41Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, GB
42Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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M Preisig
31Department of Psychiatry, University Hospital of Lausanne, Prilly, Vaud, CH
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S Ripke
32Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, US
33Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, DE
34Medical and Population Genetics, Broad Institute, Cambridge, MA, US
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SI Shyn
35Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, US
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PF Sullivan
36Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE
37Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, US
38Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, US
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J Whitfield
24Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, AU
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NR Wray
39Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, AU
40Queensland Brain Institute, The University of Queensland, Brisbane, QLD, AU
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AM McIntosh
3Division of Psychiatry, University of Edinburgh, Edinburgh, UK
41Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, GB
29Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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IJ Deary
41Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, GB
43Department of Psychology, University of Edinburgh, Edinburgh, UK
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G Breen
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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CM Lewis
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
2NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
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Abstract

Introduction It’s imperative to understand the specific and shared aetiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression.

Methods Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic aetiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in eleven data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank.

Results All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression.

Conclusions The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic aetiology irrespective of the age depression first presents.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 24, 2019.
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Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression
SP Hagenaars, JRI Coleman, S Choi, H Gaspar, MJ Adams, D Howard, K Hodgson, M Traylor, TM Air, TFM Andlauer, V Arolt, BT Baune, EB Binder, DHR Blackwood, DI Boomsma, A Campbell, M Cearns, D Czamara, U Dannlowski, K Domschke, EJC de Geus, SP Hamilton, C Hayward, I Hickie, JJ Hottenga, M Ising, I Jones, LA Jones, Z Kutalik, S Lucae, NG Martin, Y Milaneschi, B Mueller-Myhsok, MJ Owen, S Padmanabhan, BWJH Penninx, G Pistis, DJ Porteous, M Preisig, S Ripke, SI Shyn, PF Sullivan, J Whitfield, NR Wray, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, MEGASTROKE consortium, AM McIntosh, IJ Deary, G Breen, CM Lewis
bioRxiv 645077; doi: https://doi.org/10.1101/645077
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Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression
SP Hagenaars, JRI Coleman, S Choi, H Gaspar, MJ Adams, D Howard, K Hodgson, M Traylor, TM Air, TFM Andlauer, V Arolt, BT Baune, EB Binder, DHR Blackwood, DI Boomsma, A Campbell, M Cearns, D Czamara, U Dannlowski, K Domschke, EJC de Geus, SP Hamilton, C Hayward, I Hickie, JJ Hottenga, M Ising, I Jones, LA Jones, Z Kutalik, S Lucae, NG Martin, Y Milaneschi, B Mueller-Myhsok, MJ Owen, S Padmanabhan, BWJH Penninx, G Pistis, DJ Porteous, M Preisig, S Ripke, SI Shyn, PF Sullivan, J Whitfield, NR Wray, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, MEGASTROKE consortium, AM McIntosh, IJ Deary, G Breen, CM Lewis
bioRxiv 645077; doi: https://doi.org/10.1101/645077

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