Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30718454
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
2019 02 04
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