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Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
dc.contributor.author | Mullins, N. | |
dc.contributor.author | Rivera Sánchez, Margarita | |
dc.date.accessioned | 2020-10-30T11:53:57Z | |
dc.date.available | 2020-10-30T11:53:57Z | |
dc.date.issued | 2015-11-03 | |
dc.identifier.citation | 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] | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/63976 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | Medical Research Council UK (MRC) G0701420 | es_ES |
dc.description.sponsorship | GlaxoSmithKline G0701420 | es_ES |
dc.description.sponsorship | National Institute for Health Research (NIHR) | es_ES |
dc.description.sponsorship | Maudsley NHS Foundation Trust | es_ES |
dc.description.sponsorship | Institute of Psychiatry, Psychology and Neuroscience, King's College London | es_ES |
dc.description.sponsorship | European Commission Framework 6 grant (EC) LSHB-CT-2003-503428 | es_ES |
dc.description.sponsorship | 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 | es_ES |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) 5RC2MH089916 | es_ES |
dc.description.sponsorship | European Community (EC) 286213 | es_ES |
dc.description.sponsorship | MQ Fellows Award MQ14F40 | es_ES |
dc.description.sponsorship | Canada Research Chairs | es_ES |
dc.description.sponsorship | Medical Research Council UK (MRC) G0701420 1242800 MR/L010305/1 G1002366 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Cambridge University Press | es_ES |
dc.rights | Atribución 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Depression | es_ES |
dc.subject | Genetics | es_ES |
dc.subject | Gene-environment interactions | es_ES |
dc.subject | Polygenic risk scoring | es_ES |
dc.title | Polygenic interactions with environmental adversity in the aetiology of major depressive disorder | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.1017/S0033291715002172 | |
dc.type.hasVersion | VoR | es_ES |