Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample.
Case-cohort studies
Depression
GXE
Genetics
Register-based research
Stress
Journal
Biological psychiatry global open science
ISSN: 2667-1743
Titre abrégé: Biol Psychiatry Glob Open Sci
Pays: United States
ID NLM: 9918227369306676
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
04
08
2021
revised:
29
10
2021
accepted:
01
11
2021
entrez:
3
11
2022
pubmed:
4
11
2022
medline:
4
11
2022
Statut:
epublish
Résumé
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. 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. The GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide-significant ( 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.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
The GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide-significant (
Conclusions
UNASSIGNED
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.
Identifiants
pubmed: 36324662
doi: 10.1016/j.bpsgos.2021.11.003
pii: S2667-1743(21)00130-0
pmc: PMC9616262
doi:
Types de publication
Journal Article
Langues
eng
Pagination
400-410Informations de copyright
© 2021 The Authors.
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