|
PMID |
|
|
TITLE |
|
Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland. |
|
ABSTRACT |
|
|
|
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. |
|
DATE PUBLISHED |
|
|
HISTORY |
|
PUBSTATUS |
PUBSTATUSDATE |
received |
2018/11/26 |
accepted |
2018/12/10 |
entrez |
2019/02/06 06:00 |
pubmed |
2019/02/06 06:00 |
medline |
2019/06/14 06:00 |
|
AUTHORS |
|
NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Arnau-Soler A |
|
Arnau-Soler |
Aleix |
A |
|
Medical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK. aleix.arnau.soler@igmm.ed.ac.uk. |
Macdonald-Dunlop E |
|
Macdonald-Dunlop |
Erin |
E |
|
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, UK. |
Adams MJ |
|
Adams |
Mark J |
MJ |
|
Division of Psychiatry, Deanery of Clinical Sciences, Univ×ersity of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK. |
Clarke TK |
|
Clarke |
Toni-Kim |
TK |
|
Division of Psychiatry, Deanery of Clinical Sciences, Univ×ersity of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK. |
MacIntyre DJ |
|
MacIntyre |
Donald J |
DJ |
|
Division of Psychiatry, Deanery of Clinical Sciences, Univ×ersity of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK. |
Milburn K |
|
Milburn |
Keith |
K |
|
Health Informatics Centre, University of Dundee, Dundee, UK. |
Navrady L |
|
Navrady |
Lauren |
L |
|
Division of Psychiatry, Deanery of Clinical Sciences, Univ×ersity of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK. |
|
Generation Scotland |
|
|
|
|
|
|
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
|
|
|
|
|
Hayward C |
|
Hayward |
Caroline |
C |
|
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. |
McIntosh AM |
|
McIntosh |
Andrew M |
AM |
|
Division of Psychiatry, Deanery of Clinical Sciences, Univ×ersity of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK. |
Thomson PA |
|
Thomson |
Pippa A |
PA |
|
Medical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK. Pippa.Thomson@ed.ac.uk. |
|
INVESTIGATORS |
|
|
JOURNAL |
|
VOLUME: 9 |
ISSUE: 1 |
TITLE: Translational psychiatry |
ISOABBREVIATION: Transl Psychiatry |
YEAR: 2019 |
MONTH: 02 |
DAY: 04 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 2158-3188 |
ISSNTYPE: Electronic |
|
MEDLINE JOURNAL |
|
MEDLINETA: Transl Psychiatry |
COUNTRY: United States |
ISSNLINKING: 2158-3188 |
NLMUNIQUEID: 101562664 |
|
PUBLICATION TYPE |
|
PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
|
COMMENTS AND CORRECTIONS |
|
|
GRANTS |
|
GRANTID |
AGENCY |
COUNTRY |
MC_UU_00007/10 |
Medical Research Council |
United Kingdom |
104036/Z/14/Z |
Wellcome Trust |
United Kingdom |
MC_QA137853 |
Medical Research Council |
United Kingdom |
CZD/16/6 |
Chief Scientist Office |
United Kingdom |
MR/K026992/1 |
Medical Research Council |
United Kingdom |
U01 MH109528 |
NIMH NIH HHS |
United States |
U01 MH109536 |
NIMH NIH HHS |
United States |
MC_PC_17228 |
Medical Research Council |
United Kingdom |
|
GENERAL NOTE |
|
|
KEYWORDS |
|
|
MESH HEADINGS |
|
DESCRIPTORNAME |
QUALIFIERNAME |
Biological Specimen Banks |
|
Cohort Studies |
|
Depression |
genetics |
Depressive Disorder, Major |
genetics |
Female |
genetics |
Gene-Environment Interaction |
genetics |
Genetic Predisposition to Disease |
genetics |
Genome-Wide Association Study |
genetics |
Humans |
genetics |
Life Change Events |
genetics |
Male |
genetics |
Multifactorial Inheritance |
genetics |
Polymorphism, Single Nucleotide |
genetics |
Regression Analysis |
genetics |
Scotland |
genetics |
United Kingdom |
genetics |
|
SUPPLEMENTARY MESH |
|
|
GENE SYMBOLS |
|
|
CHEMICALS |
|
|
OTHER ID's |
|
|
|