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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
The Australian Genetics of Depression Study: New Risk Loci and Dissecting Heterogeneity Between Subtypes
Biological Psychiatry, Volume 92, No. 3, Year 2022
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Description
Background: Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder, but little is known about the genetic characterization of this heterogeneity. Understanding the genetic etiology of MDD can be challenging because large sample sizes are needed for gene discovery—often achieved with a trade-off in the depth of phenotyping. Methods: The Australian Genetics of Depression Study is the largest stand-alone depression cohort with both genetic data and in-depth phenotyping and comprises a total of 15,792 participants of European ancestry, 92% of whom met diagnostic criteria for MDD. We leveraged the unique nature of this cohort to conduct a meta-analysis with the largest publicly available depression genome-wide association study to date and subsequently used polygenic scores to investigate genetic heterogeneity across various clinical subtypes of MDD. Results: We increased the number of known genome-wide significant variants associated with depression from 103 to 126 and found evidence of association of novel genes implicated in neuronal development. We found that a polygenic score for depression explained 5.7% of variance in MDD liability in our sample. Finally, we found strong support for genetic heterogeneity in depression with differential associations of multiple psychiatric and comorbid traits with age of onset, longitudinal course, and various subtypes of MDD. Conclusions: Until now, this degree of detailed phenotyping in such a large sample of MDD cases has not been possible. Along with the discovery of novel loci, we provide support for differential pathways to illness models that recognize the overlap with other common psychiatric disorders as well as pathophysiological differences. © 2021 Society of Biological Psychiatry
Authors & Co-Authors
Campos, Adrian I.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Australia, Brisbane
The University of Queensland
Whiteman, David C.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Olsen, Catherine M.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Gordon, Scott D.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Dean, Olívia May
Australia, Geelong
Barwon Health
Australia, Melbourne
The Florey
Berk, Michael
Australia, Geelong
Barwon Health
Australia, Melbourne
The Florey
Australia, Melbourne
Orygen Youth Health
Hickie, I. Bernard
Australia, Sydney
The University of Sydney
Medland, Sarah E.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Wray, Naomi R.
Australia, Brisbane
The University of Queensland
Martin, Nicholas G.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Byrne, Enda M.
Australia, Brisbane
The University of Queensland
Statistics
Citations: 8
Authors: 11
Affiliations: 7
Identifiers
Doi:
10.1016/j.biopsych.2021.10.021
ISSN:
00063223
Research Areas
Genetics And Genomics
Mental Health
Study Design
Cohort Study
Study Approach
Qualitative
Systematic review