Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
Metadata
Show full item recordEditorial
Cambridge University Press
Materia
Depression Genetics Gene-environment interactions Polygenic risk scoring
Date
2015-11-03Referencia bibliográfica
Mullins, N., Power, R. A., Fisher, H. L., Hanscombe, K. B., Euesden, J., Iniesta, R., ... & Uher, R. (2016). Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychological medicine, 46(4), 759-770. [DOI: 10.1017/S0033291715002172]
Sponsorship
Medical Research Council UK (MRC) G0701420; GlaxoSmithKline G0701420; National Institute for Health Research (NIHR); Maudsley NHS Foundation Trust; Institute of Psychiatry, Psychology and Neuroscience, King's College London; European Commission Framework 6 grant (EC) LSHB-CT-2003-503428; United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) MH061686 MH059542 MH075131 MH059552 MH059541 MH060912; United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) 5RC2MH089916; European Community (EC) 286213; MQ Fellows Award MQ14F40; Canada Research Chairs; Medical Research Council UK (MRC) G0701420 1242800 MR/L010305/1 G1002366Abstract
Background. 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.
Method. 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.
Results. 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.
Conclusions. 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.