Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland.

Transl Psychiatry 2019 02 4;9(1):14. Epub 2019 Feb 4.

Medical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-018-0360-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361928PMC
February 2019
3 Reads

Publication Analysis

Top Keywords

depressive symptoms
16
interaction studies
8
genome-wide environment
8
environment interaction
8
generation scotland
8
studies gweis
4
dcc acss3
4
gweis depressive
4
biobank dcc
4
stressful life
4
symptoms genome-wide
4
symptoms stressful
4
studies gwas
4
link performed
4
acss3 drd2
4
performed genome-wide
4
genome-wide association
4
life events
4
association studies
4
gwas depressive
4

References

(Supplied by CrossRef)

R Plomin et al.
Science 1994

KS Kendler et al.
Am. J. Psychiatry 1986

KS Kendler et al.
Psychol. Med. 2007

L Colodro-Conde et al.
Mol. Psychiatry 2017

M Luciano et al.
Intelligence 2010

RC Kessler et al.
Annu. Rev. Public Health 2013

PF Sullivan et al.
Am. J. Psychiatry 2000

C Hammen et al.
Annu. Rev. Clin. Psychol. 2005

RC Kessler et al.
Annu. Rev. Psychol. 1997

KS Kendler et al.
Am. J. Psychiatry 1999

CB Stroud et al.
J. Abnorm. Psychol. 2008

Similar Publications