| Title: | Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample |
| Journal: | Biological Psychiatry Global Open Science |
| Published: | 9 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36324662/ |
| DOI: | https://doi.org/10.1016/j.bpsgos.2021.11.003 |
| Citations: | 6 (6 in last 2 years) as of 8 Aug 2024 |
Publication 12663
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Abstract
Background: Researchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results.</p>
Methods: We conducted a genome-wide by environment interaction study (GWEIS) in 18,532 patients with depression from hospital-based settings and 20,184 population controls. All individuals were drawn from the iPSYCH2012 case-cohort study, a nationally representative sample identified from Danish national registers. Information on stressful life events including family disruption, serious medical illness, death of a first-degree relative, parental disability, and child maltreatment was identified from the registers and operationalized as a time-varying count variable. Hazard ratios for main and interaction effects were estimated using Cox regressions weighted to accommodate the case-cohort design. Our replication sample included 22,880 depression cases and 50,378 controls from the UK Biobank.</p>
Results: The GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide-significant (p < 5 × 10-8) loci located in the ABCC1 gene (rs56076205, p = 3.7 × 10-10), the AKAP6 gene (rs3784187, p = 1.2 × 10-8), and near the MFSD1 gene (rs340315, p = 4.5 × 10-8). No hits replicated in the UK Biobank (rs56076205: p = .87; rs3784187: p = .93; rs340315: p = .71).</p>
Conclusions: In this large, population-based GWEIS, we did not find any replicable hits for interaction. Future gene-by-stress research in depression should focus on establishing even larger collaborative GWEISs to attain sufficient power.</p>
23 Authors
- Nis P. Suppli
- Klaus K. Andersen
- Esben Agerbo
- Veera M. Rajagopal
- Vivek Appadurai
- Jonathan R.I. Coleman
- Gerome Breen
- Jonas Bybjerg-Grauholm
- Marie Bækvad-Hansen
- Carsten B. Pedersen
- Marianne G. Pedersen
- Wesley K. Thompson
- Trine Munk-Olsen
- Michael E. Benros
- Thomas D. Als
- Jakob Grove
- Thomas Werge
- Anders D. Børglum
- David M. Hougaard
- Ole Mors
- Merete Nordentoft
- Preben B. Mortensen
- Katherine L. Musliner
1 Application
| Application ID | Title |
|---|---|
| 16577 | Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders. |
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