TY - JOUR T1 - Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder and schizophrenia JF - bioRxiv DO - 10.1101/117796 SP - 117796 AU - Joey Ward AU - Rona J. Strawbridge AU - Mark E. S. Bailey AU - Nicholas Graham AU - Amy Ferguson AU - Donald M. Lyall AU - Breda Cullen DClinPsy AU - Laura M. Pidgeon AU - Jonathan Cavanagh AU - Daniel F. Mackay AU - Jill P. Pell AU - Michael O’Donovan AU - Valentina Escott-Price AU - Daniel J. Smith Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/07/117796.abstract N2 - Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria (RDoC) 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 major depressive disorder (MDD), bipolar disorder (BD), schizophrenia and attention deficit hyperactivity disorder (ADHD). 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 eight, nine, 14 and 18), and a common single nucleotide polymorphism (SNP)-based heritability estimate of approximately 8%. We found a strong genetic correlation between mood instability and MDD (rg=0.60, SE=0.07, p=8.95x10−17) and a small but significant genetic correlation with schizophrenia (rg=0.11, SE=0.04, p=0.01), but no genetic correlation with BD or ADHD. Several genes at the associated loci may have a role in mood instability, including the deleted in colorectal cancer (DCC) gene, eukaryotic initiation factor 2B (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. ER -