Study Report

Reference	Kim, S. H.,2011 PMID: 22089088
Citation	Kim, S. H., J. Y. Song, et al. (2011). "Genetic association of the EGR2 gene with bipolar disorder in Korea." Exp Mol Med.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	946 subjects(350 healthy controls, 352 patients with BD, and 244 with SZ)
SNP/Region/Marker Size	9 SNPs
Predominant Ethnicity	Mongloid
Population	Korean
Gender	Male/female:149/203 in BD patients ,147/97 in SZ patients and 174/176 in controls
Age Group	Adults : Mean age(SD)(year):33.5(12.0) in BD patients ,32.7(7.8) in SZ patients and 25.9(6.5) in controls

Sample Diagnosis	DSM
Sample Status	Patients were interviewed individually by trained researchers using the Korean translation of the Diagnostic Interview for Genetic Studies (DIGS) (Joo et al., 2004). Meetings with at least two psychiatrists were held regularly to arrive at consensual decisions about the participants' final diagnoses and to eliminate subjects with organic brain disease, alcohol or drug problems, or other general medical conditions possibly manifesting as psychiatric symptoms. Healthy subjects included in the control group were recruited from hospital staff members and college students who volunteered to participate. Interviews conducted by a psychiatrist enabled the exclusion of subjects with histories or current evidence of psychiatric illnesses, organic mental disorders, substance abuse, or any medical conditions that might lead to mental symptoms. Control subjects who had any first-degree relatives with suspected psychiatric illnesses were also excluded. All subjects in this study were unrelated.
Technique	genotyping
Statistical Method	Contingency chi-square tests or Fisher's exact test were performed to compare allele and genotype frequencies between patients and controls.Haplotype frequencies and the significance of haplotype associations were calculated with Haploview.
Result Summary	Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contrast, no significant associations were found with SPR. Although an extended analysis with a larger sample size or independent replication is required, these findings suggest a genetic association of EGR2 with BD. Combined with a plausible biological function of EGR2, the EGR2 gene is a possible susceptibility gene in BD.