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

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  • Nis P Suppli, Københavns Universitet, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Klaus K Andersen, Kræftens Bekæmpelse
  • ,
  • Esben Agerbo
  • Veera M Rajagopal, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Vivek Appadurai, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Mental Health Services in Capital Region of Denmark
  • ,
  • Jonathan R I Coleman, King's College London, South London and Maudsley National Health Service (NHS) Trust
  • ,
  • Gerome Breen, King's College London
  • ,
  • Jonas Bybjerg-Grauholm, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Marie Bækvad-Hansen, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut
  • ,
  • Carsten B Pedersen
  • Marianne G Pedersen
  • Wesley K Thompson, University of California at San Diego, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Trine Munk-Olsen
  • Michael E Benros, Københavns Universitet, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
  • ,
  • Thomas D Als
  • Jakob Grove
  • Thomas Werge, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Region Hovedstaden
  • ,
  • Anders D Børglum
  • David M Hougaard, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Statens Serum Institut
  • ,
  • Ole Mors
  • Merete Nordentoft, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Københavns Universitet
  • ,
  • Preben B Mortensen
  • Katherine L Musliner

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.

OriginalsprogEngelsk
TidsskriftBiological Psychiatry: Global Open Science
Vol/bind2
Nummer4
Sider (fra-til)400-410
Antal sider11
ISSN2667-1743
DOI
StatusUdgivet - okt. 2022

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© 2021 The Authors.

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