RT Journal Article
SR Electronic
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
FD Cold Spring Harbor Laboratory
SP 117796
DO 10.1101/117796
A1 Joey Ward
A1 Rona J. Strawbridge
A1 Mark E. S. Bailey
A1 Nicholas Graham
A1 Amy Ferguson
A1 Donald M. Lyall
A1 Breda Cullen DClinPsy
A1 Laura M. Pidgeon
A1 Jonathan Cavanagh
A1 Daniel F. Mackay
A1 Jill P. Pell
A1 Michael O’Donovan
A1 Valentina Escott-Price
A1 Daniel J. Smith
YR 2017
UL http://biorxiv.org/content/early/2017/04/07/117796.abstract
AB 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.