Format

Send to

Choose Destination
Psychol Med. 2016 Mar;46(4):759-70. doi: 10.1017/S0033291715002172. Epub 2015 Nov 3.

Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.

Author information

1
MRC Social, Genetic and Developmental Psychiatry Centre,Institute of Psychiatry, Psychology & Neuroscience,King's College London,London,UK.
2
Division of Genetics and Molecular Medicine,King's College London School of Medicine,Guy's Hospital,London,UK.
3
Department of Psychiatry and Behavioral Sciences,Stanford University,Stanford, CA,USA.
4
Department of Psychiatry,Columbia University and New York State Psychiatric Institute,New York, NY,USA.
5
Department of Psychiatry,University of Iowa,Iowa City, IA,USA.
6
Division of Cancer Epidemiology and Genetics,National Cancer Institute,Bethesda, MD,USA.
7
Discipline of Psychiatry,School of Medicine,University of Adelaide,Adelaide,South Australia,Australia.
8
Department of Psychiatry,School of Clinical and Experimental Medicine,University of Birmingham,Birmingham,UK.
9
MRC Centre for Neuropsychiatric Genetics and Genomics,Neuroscience and Mental Health Research Institute,Cardiff University,Cardiff,UK.
10
Barts and The London Medical School,Queen Mary University of London,London,UK.

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.

KEYWORDS:

Depression; gene-environment interactions; genetics; polygenic risk scoring

PMID:
26526099
PMCID:
PMC4754832
DOI:
10.1017/S0033291715002172
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Cambridge University Press Icon for PubMed Central
Loading ...
Support Center