Study Report

Reference	Silberberg, G.,2010 PMID: 20645313
Citation	Silberberg, G., D. Ben-Shachar, et al. (2010). "Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder." Am J Med Genet B Neuropsychiatr Genet 153B(7): 1318-1328.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	35 schizophrenia patients, 35 bipolar patients, and 35 control subjects
SNP/Region/Marker Size	2 variants
Predominant Ethnicity	Caucasian
Population	Israeli

Sample Diagnosis	DSM
Sample Status	Total RNA and DNA from DLPFC samples, Brodmann area 46 was donated by the Stanley Foundation Array Collection (Bethesda, Maryland).The collection includes 35 schizophrenia patients, 35 bipolar patients, and 35 control subjects who were well matched for age,pH, and gender [Torrey et al., 2000]. Additional information and exclusion criteria of samples for the Stanley Array were described by the Stanley Medical Research Institute (http://www.stanleyresearch.org/dnn/Default.aspx?tabid=89).
Technique	PCR and RFLP
Statistical Method	Descriptive statistics, means comparisons,univariate GLM, and correlations were analyzed by the SPSS 14.0 program (SPSS, Chicago, IL). The Bonferroni post hoc test was used for multiple group comparisons.
Result Summary	For the Danish population, association was suggested between silent SNP G573A and BPAD (P = 0.008). For the British population we found association to BPAD with missense mutation Leu48Met (P = 0.003) and missense mutation Pro335Leu (P = 0.004). The statistical significance of the association was, however, greatly reduced after correcting for multiple testing. When combining genotypes from Leu48Met and Pro335Leu into haplotypes, association to BPAD was found in the British population (P = 0.0007). This haplotype association was not replicated in the Danish population. Our results may indicate that the SSTR5 gene is involved in the etiology of BPAD or may exist in linkage disequilibrium with a susceptibility gene close to SSTR5. However, given the marginal statistical significance and the potential for false-positive results in association studies with candidate genes, further studies are needed to clarify this hypothesis.