Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD and a small but significant genetic correlation with both schizophrenia and anxiety disorders, although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.
Genome-wide association studies of mental health.
The primary aim of this research is to identify genetic associations with a) major depression plus mania/bipolar disorder, and b) vulnerability to depression and other negative mood states (as measured by neuroticism score). These aims will be achieved by conducting genome-wide association studies (GWAS), making use of data from the UK Biobank genotyping project. This project is linked to previous analyses our team have undertaken on Biobank data in the areas of mood disorder, cognitive function, cardiometabolic disease and ethnicity and meets Biobank?s stated purpose of improving the prevention, diagnosis and treatment of illnesses by identifying genetic risk factors for common mental disorders, as well as genetic risk factors for trait-like vulnerability to these disorders (neuroticism). Insights from this work will lead to a better understanding of disease processes in depression, better approaches to diagnosis and ultimately the development of new treatments. This work will consist of genome-wide association studies (GWAS), making use of data from the UK Biobank genotyping project. These GWAS studies on depression and neuroticism will make use of phenotypic and genetic data on all Biobank participants (full cohort).
|Lead investigator:||Dr Rona Strawbridge|
|Lead institution:||University of Glasgow|
9 related Returns
|Return ID||App ID||Description||Archive Date|
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|1981||6553||Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort||10 Feb 2020|
|2524||6553||Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide||23 Oct 2020|
|3378||6553||Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure||26 Apr 2021|
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|3888||6553||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||29 Sep 2021|
|3884||6553||The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically diferent groups of individuals||29 Sep 2021|
|1964||Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia||Ward, J et al||2020||Translational Psychiatry|