| Title: | Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters |
| Journal: | Journal of Affective Disorders |
| Published: | 26 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38806065/ |
| DOI: | https://doi.org/10.1016/j.jad.2024.05.126 |
| URL: | https://www.sciencedirect.com/science/article/pii/S016503272400870X |
Publication 11979
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Abstract
BACKGROUND: Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters.</p>
METHODS: We analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP × CTS interaction effects on the participants' cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G × E studies for childhood maltreatment's association with depression.</p>
RESULTS: At SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, MPST and PRH2 were genome-wide significant for the low-multimorbidity Clusters 1 and 3, respectively. Regarding candidate SNPs for G × E interactions, individual SNP results could be replicated for specific clusters. The candidate genes CREB1, DBH, and MTHFR (Cluster 5) as well as TPH1 (Cluster 6) survived multiple testing correction.</p>
LIMITATIONS: CTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders.</p>
CONCLUSIONS: The first G × E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G × E studies related to depression, and revealed risk clusters for the contribution of childhood trauma.</p>
15 Keywords
- Adult
- Adverse Childhood Experiences
- Aged
- Depressive Disorder, Major
- Female
- Gene-Environment Interaction
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Multimorbidity
- Polymorphism, Single Nucleotide
- Risk Factors
- United Kingdom
11 Authors
- Sarah Bonk
- Nora Eszlari
- Kevin Kirchner
- Andras Gezsi
- Linda Garvert
- Mikko Kuokkanen
- Isaac Cano
- Hans J Grabe
- Peter Antal
- Gabriella Juhasz
- Sandra Van der Auwera
1 Application
| Application ID | Title |
|---|---|
| 1602 | Association between diet and depression |
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