Study Report

Reference	Green EK, 2013 PMID: 22565781
Citation	Green, E. K., D. Grozeva, et al. (2013). "Association at SYNE1 in both bipolar disorder and recurrent major depression." Mol Psychiatry 18(5): 614-617.
Disease Type	bipolar disorder & unipolar depression
Study Design	case-control
Study Type	Candidate-gene association study and Meta-analysis
Sample Size	1527 BD cases, 1159 MDD cases and 2592 controls
SNP/Region/Marker Size	1 SNP
Predominant Ethnicity	Caucasian
Population	British
Gender	24% male for BD cases, 34% male for MDD cases, 50% male controls
Age Group	adults : a mean age at first impairment of 22 (s.d. 9) years of BD cases, mean age 48 (s.d. 13) years of MDD cases

Sample Diagnosis	Research Diagnostic Criteria for BD cases, DSM-IV criteria for unipolar recurrent major depression cases
Sample Status	BD cases: the individuals were recruited if they suffered with a major mood disorder, in which clinically significant episodes of elevated mood had occurred. This was defined as a lifetime diagnosis of a bipolar mood disorder according to Research Diagnostic Criteria,19 and included bipolar I disorder (63% cases), bipolar II disorder (29% cases), schizoaffective disorder and bipolar type (8% cases). Unipolar recurrent major depression cases: unipolar cases were also excluded if they (i) had a first- or second-degree relative with a diagnosis of bipolar affective disorder or SZ, schizotypal disorder, persistent delusional disorder, acute and transient psychotic disorders, or schizoaffective disorder (all of which increase the likelihood of developing BD or a psychotic disorder); or (ii) had ever experienced mood-incongruent psychosis or psychosis outside of mood episodes.
Technique	Individual genotyping was performed using the Sequenom MassARRAY iPlex platform (Sequenom, San Diego, CA, USA).
Statistical Method	Single-locus association test (Cochran--Armitage Trend test) and assessment of marker Hardy-Weinberg equilibrium in the association samples were performed using PLINK 1.07.Results of meta-analysis were combined by fixed-effects meta-analyses using PLINK 1.07 to estimate a common odds ratio (OR) weighted by individual study's standard error.
Result Summary	Here we have tested this polymorphism in an independent BD case (n=1527) and control (n=1579) samples, and find evidence for association (P=0.0095) with similar effect sizes to those previously observed in BD (allelic OR=1.148). In a combined (meta) analysis of PGC-BD data (both primary and replication data) and our independent BD samples, we found genome-wide significant evidence for association (P=2.9e-8, OR=1.104). We have also examined the polymorphism in our recurrent unipolar depression cases (n=1159) and control (n=2592) sample, and found that the risk allele was associated with risk for recurrent major depression (P=0.032, OR=1.118). Our findings add to the evidence that association at this locus influences susceptibility to bipolar and unipolar mood disorders.