Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression.,American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

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Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ( IF 1.6 ) Pub Date : 2020-07-18 , DOI: 10.1002/ajmg.b.32807
Saskia P Hagenaars _{1,

2} , Jonathan R I Coleman _{1,

2} , Shing Wan Choi ₁ , Héléna Gaspar _{1,

2} , Mark J Adams ₃ , David M Howard _{1,

3} , Karen Hodgson _{1,

2} , Matthew Traylor ₄ , Tracy M Air ₅ , Till F M Andlauer _{6,

7} , Volker Arolt ₈ , Bernhard T Baune _{8,

9,

10} , Elisabeth B Binder _{6,

11} , Douglas H R Blackwood ₁₂ , Dorret I Boomsma ₁₃ , Archie Campbell ₁₂ , Micah Cearns ₉ , Darina Czamara ₆ , Udo Dannlowski ₈ , Katharina Domschke _{14,

15} , Eco J C de Geus ₁₃ , Steven P Hamilton ₁₆ , Caroline Hayward _{12,

17} , Ian B Hickie ₁₈ , Jouke Jan Hottenga ₁₃ , Marcus Ising ₁₉ , Ian Jones ₂₀ , Lisa Jones ₂₁ , Zoltan Kutalik _{22,

23} , Susanne Lucae ₁₉ , Nicholas G Martin ₂₄ , Yuri Milaneschi ₂₅ , Bertram Mueller-Myhsok _{6,

26,

27} , Michael J Owen ₂₀ , Sandosh Padmanabhan _{12,

28} , Brenda W J H Penninx ₂₅ , Giorgio Pistis ₂₉ , David J Porteous ₁₂ , Martin Preisig ₂₉ , Stephan Ripke _{30,

31,

32} , Stanley I Shyn ₃₃ , Patrick F Sullivan _{34,

35,

36} , John B Whitfield ₂₄ , Naomi R Wray _{37,

38} , Andrew M McIntosh _{3,

12,

39} , Ian J Deary _{39,

40} , Gerome Breen _{1,

2} , Cathryn M Lewis _{1,

2}

Affiliation

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
NIHR Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Discipline of Medicine, University of Adelaide, Adelaide, Australia.
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Department of Psychiatry, University of Münster, Münster, Germany.
Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, Australia.
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Netherlands Twin Register, Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands.
Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Psychiatry, Kaiser Permanente Northern California, San Francisco, California, USA.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Max Planck Institute of Psychiatry, Munich, Germany.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Department of Psychological Medicine, University of Worcester, Worcester, UK.
Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience Research Institutes, Amsterdam UMC/Vrije Universiteit, Amsterdam, The Netherlands.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Department of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Maryland, USA.
Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Behavioral Health Services, Kaiser Permanente Washington, Seattle, Washington, USA.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.

It is imperative to understand the specific and shared etiologies 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. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology 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 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. 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. The phenotypic associations between major depression and cardio‐metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.

中文翻译：

重度抑郁症和心脏代谢特征之间的遗传共病，按重度抑郁症发病年龄分层。

必须了解重度抑郁症和心脏代谢疾病的具体和共同病因，因为这两种特征经常共存，并且每种特征都对社会造成重大负担。这项研究探讨了重度抑郁症与心脏代谢特征之间是否存在遗传关联，以及这种关联是否按重度抑郁症发病年龄进行分层。进行多基因风险评分分析和连锁不平衡评分回归，以检查抑郁症病例控制状态（ N例 = 40,940， N对照 = 67,532）、早期发病抑郁症（ N = 15,844）和晚发抑郁症（ N ）之间是否存在共同遗传病因学差异。 = 15,800），包括来自精神病基因组学联盟、苏格兰一代和英国生物银行的 11 个数据集中的体重指数、冠状动脉疾病、中风和 2 型糖尿病。所有心脏代谢多基因风险评分均与抑郁状态相关。研究发现抑郁症与体重指数、冠状动脉疾病和 2 型糖尿病之间存在显着的遗传相关性。体重指数、冠状动脉疾病和 2 型糖尿病的较高多基因风险与早发和晚发抑郁症相关，而中风的较高多基因风险仅与晚发抑郁症相关。体重指数与晚发性抑郁症之间以及冠状动脉疾病与早发性和晚发性抑郁症之间发现了显着的遗传相关性。重度抑郁症和心脏代谢特征之间的表型关联可能部分反映了它们重叠的遗传病因学，无论抑郁症首次出现的年龄如何。

更新日期：2020-08-08

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