Study Report

Reference	Szczepankiewicz A., 2014 PMID: 24856550
Citation	Szczepankiewicz, A., et al. (2014). "FKBP5 polymorphism is associated with major depression but not with bipolar disorder." J Affect Disord 164: 33-37.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Genetic interaction study
Sample Size	528 bipolar patients, 218 patients with major depressive disorder and 742 subjects from control group
SNP/Region/Marker Size	8 SNPs
Predominant Ethnicity	Caucasian
Population	Wielkopolska
Gender	BD: 41.8% male of 528 BD patients; MDD: 23.0% male of 218 MDD patients; Controls: 42.5% male of 742 controls.
Age Group	adults : BD: mean=44.36, SD=13.9; MDD: mean=45.5, SD=14.0; Controls: mean=37.7, SD=12.5

Sample Diagnosis	DSM-IV
Sample Status	Patients were recruited from inpatients from Wielkopolska region, considered as ethnically homogenous, treated at the Department of Psychiatry, University of Medical Sciences in Poznan. Consensus lifetime diagnosis by two experienced psychiatrists was made for each patient. The phenotyping was based on clinical interviews, medical records and family history method according to DSM-IV criteria using SCID (Structured Clinical Interview for DSM Disorders). All relevant clinical information regarding the course of both disorders were provided by SCID.
Technique	genotyped with use of TaqMan SNP Genotyping assays (Applied Biosystems) and TaqMan Genotyping Master Mix.
Statistical Method	The two-tailed Pearson's chi-square (_2) test and Fisher's exact test were used to test differences in the genotypic and allelic (respectively) distribution between the groups of patients and control subjects. Odds ratios were calculated using 2*2 contingency tables with use of Fisher's exact test in a demo version of GraphPad InStat 3 software. Linkage disequilibrium (LD) between SNPs polymorphisms within FKBP5 gene was examined by pair-wise comparisons of r2 and D' using Haploview version 4.1. Correction for multiple testing was performed for multiple comparisons in haplotype analysis and was done by 10 000 permutations. Higher-order gene-gene interactions among tested SNPs of FKBP5 and NR3C1 were analyzed using the non-parametric and genetic model-free Multifactor Dimensionality Reduction (MDR) approach (v.2.0 beta 8.3). Statistical significance was determined using a 1000-fold permutation test (MDR permutation testing module v.1.0 beta 2).
Result Summary	We have observed an association between five FKBP5 polymorphisms (rs1360780, rs9470080, rs4713916, rs9296158 and rs9394309) and major depressive disorder (p=0.011; p=0.007, p=0.038; p=0.030; p=0.018, respectively), but not bipolar disorder. In linkage disequilibrium analysis we found that seven FKBP5 polymorphisms build haplotype block (rs3800373, rs755658, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080, respectively). We observed that two haplotype combinations (ACATTGT and CCACTAT) were significantly more frequent in the MDD patients than in controls (p=0.014 and p=0.043). We have not observed such an association for BD patients. We have found that interaction between rs9470080 of FKBP5 and rs6198 of NR3C1 influences MDD risk.