Abstract
The utilization of molecular genetics approaches in examination of panic
disorder (PD) has implicated several variants as potential
susceptibility factors for panicogenesis. However, the identification of
robust PD susceptibility genes has been complicated by phenotypic
diversity, underpowered association studies and ancestry-specific
effects. In the present study, we performed a succinct review of
case-control association studies published prior to April 2015.
Meta-analyses were performed for candidate gene variants examined in at
least three studies using the Cochrane Mantel-Haenszel fixed-effect
model. Secondary analyses were also performed to assess the influences
of sex, agoraphobia co-morbidity and ancestry-specific effects on
panicogenesis. Meta-analyses were performed on 23 variants in 20 PD
candidate genes. Significant associations after correction for multiple
testing were observed for three variants, TMEM132D rs7370927 (T allele:
odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.15-1.40, P =
2.49 x 10(-6)), rs11060369 (CC genotype: OR = 0.65, 95% CI: 0.53-0.79, P
= 1.81 x 10(-5)) and COMT rs4680 (Val (G) allele: OR = 1.27, 95% CI:
1.14-1.42, P = 2.49 x 10(-5)) in studies with samples of European
ancestry. Nominal associations that did not survive correction for
multiple testing were observed for NPSR1 rs324891 (T allele: OR = 1.22,
95% CI: 1.07-1.38, P = 0.002), TPH1 rs1800532 (AA genotype: OR = 1.46,
95% CI: 1.14-1.89, P = 0.003) and HTR2A rs6313 (T allele: OR = 1.19, 95%
CI: 1.07-1.33, P = 0.002) in studies with samples of European ancestry
and for MAOA-uVNTR in female PD (low-active alleles: OR = 1.21, 95% CI:
1.07-1.38, P = 0.004). No significant associations were observed in the
secondary analyses considering sex, agoraphobia co-morbidity and studies
with samples of Asian ancestry. Although these findings highlight a few
associations, PD likely involves genetic variation in a multitude of
biological pathways that is diverse among populations. Future studies
must incorporate larger sample sizes and genome-wide approaches to
further quantify the observed genetic variation among populations and
subphenotypes of PD.
