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Genome-by-Trauma Exposure Interactions in Adults With Depression in the UK Biobank
Melisa Chuong1,2, Mark J Adams2, Alex S F Kwong2
1Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, United Kingdom.
JAMA Psychiatry
|September 28, 2022
Summary
Trauma exposure significantly interacts with genetic factors to influence major depressive disorder (MDD) risk. Genome-by-trauma interactions explain more depression variance in males, suggesting sex-specific depression causes.
Area of Science:
- Psychiatry and Genetics
- Genomics and Environmental Health
Background:
- Self-reported trauma exposure is a known risk factor for major depressive disorder (MDD).
- Previous studies explored gene-environment interactions using limited genetic data, capturing minimal phenotypic risk variance.
Purpose of the Study:
- To re-evaluate genome-by-trauma interaction associations for MDD.
- To maximize accounted variance by utilizing all available genotyped data.
Main Methods:
- Utilized UK Biobank data from 148,129 participants.
- Employed a mixed-model statistical approach with whole-genome single-nucleotide variation (SNV) data.
- Analyzed trauma exposure, depression, and neuroticism to explore variance sources.
Main Results:
- Genome-by-trauma interactions significantly accounted for MDD risk variance (0.074-0.201).
- Trauma subtypes also explained significant MDD variance (0.056-0.176).
- Interaction variance was approximately 5-fold greater for MDD in males (0.441) compared to females (0.086).
Conclusions:
- Genome-by-trauma interactions are associated with depression manifestation.
- Greater interaction variance in males suggests potential sex differences in depression etiology.
- Methodology can identify modifiable risk factors and target interventions for at-risk groups.
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