Publication: Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.
Loading...
Identifiers
Date
2015-19-22
Authors
Mullins, N
Power, R A
Fisher, H L
Hanscombe, K B
Euesden, J
Iniesta, R
Levinson, D F
Weissman, M M
Potash, J B
Shi, J
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Cambridge University Press
Abstract
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 × 10(-4) and p = 5.12 × 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.
Description
MeSH Terms
Adult
Adult Survivors of Child Adverse Events
Depressive Disorder, Major
Female
Gene-Environment Interaction
Humans
Life Change Events
Male
Middle Aged
Multifactorial Inheritance
Risk Factors
Stress, Psychological
Young Adult
Adult Survivors of Child Adverse Events
Depressive Disorder, Major
Female
Gene-Environment Interaction
Humans
Life Change Events
Male
Middle Aged
Multifactorial Inheritance
Risk Factors
Stress, Psychological
Young Adult
DeCS Terms
Trastorno depresivo mayor
Persona de mediana edad
Masculino
Interacción gen-ambiente
Herencia multifactorial
Factores de riesgo
Estrés psicológico
Adultos sobrevivientes de eventos adversos infantiles
Adulto joven
Persona de mediana edad
Masculino
Interacción gen-ambiente
Herencia multifactorial
Factores de riesgo
Estrés psicológico
Adultos sobrevivientes de eventos adversos infantiles
Adulto joven
CIE Terms
Keywords
Depression, gene-environment interactions, genetics, polygenic risk scoring
Citation
Mullins N, Power RA, Fisher HL, Hanscombe KB, Euesden J, Iniesta R, et al. Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychol Med. 2016 Mar;46(4):759-70.