Immune-related pathways including HLA-DRB1(∗)13:02 are associated with panic disorder

Abstract

Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety. Both genetic and environmental factors are thought to trigger PD onset. Previously, we performed a genome-wide association study (GWAS) for PD and focused on candidate SNPs with the lowest P values. However, there seemed to be a number of polymorphisms which did not reach genome-wide significance threshold due to their low allele frequencies and odds ratios, even though they were truly involved in pathogenesis. Therefore we performed pathway analyses in order to overcome the limitations of conventional single-marker analysis and identify associated SNPs with modest effects. Each pathway analysis indicated that pathways related to immunity showed the strongest association with PD (DAVID, P=2.08×10(-6); i-GSEA4GWAS, P<10(-3); ICSNPathway, P<10(-3)). Based on the results of pathway analyses and the previously performed GWAS for PD, we focused on and investigated HLA-B and HLA-DRB1 as candidate susceptibility genes for PD. We typed HLA-B and HLA-DRB1 in 744 subjects with PD and 1418 control subjects. Patients with PD were significantly more likely to carry HLA-DRB1(∗)13:02 (P=2.50×10(-4), odds ratio=1.54). Our study provided initial evidence that HLA-DRB1(∗)13:02 and genes involved in immune-related pathways are associated with PD. Future studies are necessary to confirm these results and clarify the underlying mechanisms causing PD.

Keywords: Genome-wide association study; HLA-B; HLA-DRB1; Human Leukocyte Antigen; Immunity; Panic disorder; Pathway analysis.