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The genetic basis of major depression

Published online by Cambridge University Press:  08 March 2021

K. M. Kendall
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
E. Van Assche
Affiliation:
Department of Psychiatry, University of Muenster, Muenster, Germany
T. F. M. Andlauer
Affiliation:
Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
K. W. Choi
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA02114, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA02114, USA Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA02115, USA
J. J. Luykx
Affiliation:
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Outpatient Second Opinion Clinic, GGNet Mental Health, Warnsveld, The Netherlands
E. C. Schulte
Affiliation:
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
Y. Lu*
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
*
Author for correspondence: Y. Lu, E-mail: lu.yi@ki.se

Abstract

Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.

Type
Invited Review
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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