Study Report

Reference	Arai, M., 2004 PMID: 15050861
Citation	Arai, M., M. Itokawa, et al. (2004). "Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals." Biol Psychiatry 55(8): 804-810.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	357 unrelated control individuals and 151 patients with bipolar disorder (66% bipolar I, 34% bipolar II) and 78 unipolar disorder
SNP/Region/Marker Size	11 SNPs
Predominant Ethnicity	Mongloid
Population	Japanese
Gender	Patients with bipolar disorder comprised 80 men and 71 women; patients with unipolar disorder comprised 33 men and 45 women; control subjects included 173 men and 184 women
Age Group	adults : Patients with bipolar disorder comprised 80 men (mean age=49.0, SD=11.9 years) and 71 women (mean age=48.9, SD=12.4 years). Patients with unipolar disorder comprised 33 men (mean age=48.1, SD=10.7 years) and 45 women (mean age =50.7, SD=10.9 years). Control subjects included 173 men (mean age=50.5, SD=13.5 years) and 184 women (mean age=52.8, SD=11.0 years).

Sample Diagnosis	DSM-IV
Technique	PCR and genotyping
Statistical Method	Departure from Hardy-Weinberg equilibrium was examined with the X2 test. Differences in genotype and allele frequencies were evaluated with Fisher's exact test or the Monte-Carlo method implemented in the CLUMP program when appropriate. Linkage disequilibrium (LD) statistics were calculated with COCAPHASE. Estimation and comparison of haplotype frequencies were made with COCAPHASE. Graphic overview of pairwise LD strength between markers was made with GOLD software. Power calculations were performed with Power Calculator.
Result Summary	Three single nucleotide polymorphisms, IVS6+32T>C, IVS7+11G>C and IVS12+21C>A, displayed significant associations with bipolar disorder (for allelic associations, nominal p =.04, p =.02, and p =.004, respectively, all p >.05 after Bonferroni corrections). Furthermore, the haplotype located in a linkage disequilibrium block was strongly associated with bipolar disorder (the p value of the most significant three-marker haplotype is .005). Our results suggest that genetic variations in NCAM1 or nearby genes could confer risks associated with bipolar affective disorder in Japanese individuals.