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Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cambridge University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754832/ https://www.ncbi.nlm.nih.gov/pubmed/26526099 http://dx.doi.org/10.1017/S0033291715002172 |
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author | 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. Uher, R. Cohen-Woods, S. Rivera, M. Jones, L. Jones, I. Craddock, N. Owen, M. J. Korszun, A. Craig, I. W. Farmer, A. E. McGuffin, P. Breen, G. Lewis, C. M. |
author_facet | 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. Uher, R. Cohen-Woods, S. Rivera, M. Jones, L. Jones, I. Craddock, N. Owen, M. J. Korszun, A. Craig, I. W. Farmer, A. E. McGuffin, P. Breen, G. Lewis, C. M. |
author_sort | Mullins, N. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4754832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47548322016-03-10 Polygenic interactions with environmental adversity in the aetiology of major depressive disorder 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. Uher, R. Cohen-Woods, S. Rivera, M. Jones, L. Jones, I. Craddock, N. Owen, M. J. Korszun, A. Craig, I. W. Farmer, A. E. McGuffin, P. Breen, G. Lewis, C. M. Psychol Med Original Articles 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. Cambridge University Press 2016-03 2015-11-03 /pmc/articles/PMC4754832/ /pubmed/26526099 http://dx.doi.org/10.1017/S0033291715002172 Text en © Cambridge University Press 2015 http://creativecommons.org/licenses/by/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles 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. Uher, R. Cohen-Woods, S. Rivera, M. Jones, L. Jones, I. Craddock, N. Owen, M. J. Korszun, A. Craig, I. W. Farmer, A. E. McGuffin, P. Breen, G. Lewis, C. M. Polygenic interactions with environmental adversity in the aetiology of major depressive disorder |
title | Polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
title_full | Polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
title_fullStr | Polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
title_full_unstemmed | Polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
title_short | Polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
title_sort | polygenic interactions with environmental adversity in the aetiology of major
depressive disorder |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754832/ https://www.ncbi.nlm.nih.gov/pubmed/26526099 http://dx.doi.org/10.1017/S0033291715002172 |
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