Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt


  • Fulltext

    Forlagets udgivne version, 1,38 MB, PDF-dokument

  • 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
  • Thomas D. Als
  • Jakob Grove
  • Anders D. Børglum
  • David M. Hougaard
  • Ole Mors
  • Preben B. Mortensen
  • Katherine L. Musliner
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 (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).

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.
TidsskriftBiological Psychiatry Global Open Science
Udgave nummer4
Sider (fra-til)400-410
Antal sider11
StatusUdgivet - 2023

ID: 291539376