PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Meta-analysis Report

Basic Info

Reference	Navarro-Mateu, F.,2013 PMID: 23825531
Citation	Navarro-Mateu, F., et al. (2013). "Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder." PLoS One 8(6): e66227.
Objective	To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases.
Study Type	Candidate gene association study,Gene-Environmental interaction study
Extract Database	PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network)
Time Range	up until December 2011

Detail Info

Samples	13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. Case status was defined as having a current or one-year DSM-III, DSM-IIIR or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) diagnosis of PTSD assessed by established psychiatric interviews. Studies of all ethnic groups were considered eligible. Reviews,case-only studies,family-based designs and population studies with only healthy subjects were excluded, as well as other studies describing genetic effects on other anxiety or depression-related phenotypes such as anxiety, depression or on different personality traits.As poor reporting quality has been associated with a biased estimation of effects in clinical intervention studies, the quality of each study selected for inclusion was assessed by applying a 12-item quality checklist, derived from the STREGA statement (Strengthening the Reporting of Genetic Association Studies) and other criteria. For more details, please refer to the article.
Statistic Method	Inter-rater agreement was measured by Cohen's kappa coefficient for inclusion and exclusion criteria. The association between the 5-HTLLPR allelic frequency and PTSD was examined by statistical analyses, firstly using the biallelic model (Biallelic Frequency Model, BFM) and then a triallelic one (Triallelic Frequency Model, TFM) by calculating the respective Odds Ratio (OR) and its corresponding 95% confidence interval (95% CI) as the effect size measurement for these analyses. Random-effects models were applied in the statistical analyses.The statistical significance of the pooled OR was assessed using the Z test.A sensitivity analysis was performed. To explore heterogeneity, different subgroup analyses, which allow chi-squared tests for between group differences, were performed taking as potential moderators the quality items,ethnicity and study design. Meta-regressions, funnel plots with the trim-and-fill method and the Egger test were calculated with the program Comprehensive Meta-analysis 2.0.
Basic Result	None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias.

Genetic result reported by this study

Normal genetic result reported by this study (count: 1)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
5-HTTLPR	PTSD	SLC6A4	S allele vs L allele: OR=1.05; 95% CI=0.87, 1.26; P-value=0.63; I²=63; the dominant model,BDM (S+vs LL)OR=1.01;95% CI=0.78, 1.30; P-value=0.95; I²=57; the recessive model, BRM (SS vs L+) OR=1.15; 95%CI=0.82, 1.60; P-value=0.41; I²=55, respectively) (Figs 2, 3 and 4).Secondly, a meta-analysis of the triallelic approach offered similar results for the TFM model (OR=1.15; 95%CI=0.82,1.60; P-value=0.41; I²=74), for TDM model (OR=1.02; 95%CI=0.73, 1.48; P-value=0.93; I²= 43) and for the TRM (OR=1.31; 95%CI=71, 2.41; P-value=0.38; I²=80) (Figs 5, 6 and 7, respectively).0.66, 1.74; I²=78% and TFM, OR=1.14; 95% CI: 0.70, 1.87; I²=81%), in the dominant model (BDM, OR=1.09; 95% CI: 0.61, 1.96; I²=72%, TDM, OR=0.93; 95% CI: 0.60, 1.44; I²=39%) and in the recessive model (BRM, OR=1.05; 95% CI: 0.41, 2.67; I²=73%, TRM, OR=1.40; 95% CI: 0.54, 3.57;I²=85%).	This is the first published meta-analysis of the relationshi...... This is the first published meta-analysis of the relationship between 5-HTTLPR polymorphisms and PTSD. They found no significant relationship between biallelic or triallelic polymorphism and PTSD, using the three possible approaches (allele frequency, dominant and recessive model). More...	Non-significant