Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function

Ward, Joey, Tunbridge, Elizabeth M., Sandor, Cynthia, Lyall, Laura M., Ferguson, Amy, Strawbridge, Rona J., Lyall, Donald M., Cullen, Breda, Graham, Nicholas, Johnston, Keira J. A., Webber, Caleb, Escott-Price, Valentina, O'Donovan, Michael, Pell, Jill P., Bailey, Mark E. S., Harrison, Paul J. and Smith, Daniel J. 2019. The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function. Molecular Psychiatry 10.1038/s41380-019-0439-8

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Springer Nature
ISSN: 1359-4184
Date of First Compliant Deposit: 19 June 2019
Date of Acceptance: 29 April 2019
Last Modified: 09 Sep 2019 08:17
URI: http://orca.cf.ac.uk/id/eprint/123563

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics