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Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample
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. METHODS: We conducted a genome-wide by environment interaction study (GWEIS) in 18,532 p...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616262/ https://www.ncbi.nlm.nih.gov/pubmed/36324662 http://dx.doi.org/10.1016/j.bpsgos.2021.11.003 |
Sumario: | 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. 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. 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). 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. |
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