Meta-analysis Report

Reference	Chen, C., 2008 PMID: 19032713
Citation	Chen, C., S. J. Glatt, et al. (2008). "The tryptophan hydroxylase gene influences risk for bipolar disorder but not major depressive disorder: results of meta-analyses." Bipolar Disord 10(7): 816-821.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Type	Candidate-gene association study

Samples	Genotype data were obtained from a total of 2,083 cases and 1,976 controls in seven independent studies of BD. Eight case-control studies provided data on a total of 1,812 cases with MDD and 2,223 control subjects.
Statistic Method	We performed our meta-analyses consistent with the methods described by Normand. Casecontrol studies were analyzed by random effects meta-analysis. The pooled OR was calculated according to the methods of DerSimonian and Laird, which weight the studies according to sample size and the degree of disparity between case and control groups, such that larger and more well-balanced studies receive more weight. The 95% confidence interval (CI) around the pooled OR was constructed using Woolf s method. The heterogeneity of each group of ORs was assessed using a chi-square test of goodness of fit; due to the low power of this test (particularly when applied to a small number of studies), we fixed the type-I error rate for the heterogeneity analyses at 0.10. The significance of each pooled OR was determined by the z-test. The influence of individual studies on the pooled OR was determined by sequentially removing each study and recalculating the pooled OR and 95% CI. Publication bias within each group of ORs was assessed by the method of Egger et al. The moderating influences of sample ancestry, age of the control group, age of the case group, and gender index on the OR derived from each study were assessed by multiple regression. The type-I error rate was set at 0.05 for all analyses unless otherwise specified. All statistical analyses were conducted using Stata SE, version 9.0 for Windows (Stata Corporation, College Station, TX, USA).
Basic Result	The AA genotype had a significant effect on risk for bipolar disorder in comparison to either the CC or AC genotypes, suggesting that the A allele may increase risk for bipolar disorder in a recessive manner. None of the three genotypes significantly increased risk for major depressive disorder relative to any of the other genotypes.