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LRRC8E, MAP2K7, 19p13.2, panic disorder, single nucleotide polymorphism, SNAPC2
Abstract:
Panic disorder (PD) is a severe and disabling mental disorder, which is
moderately heritable. In a previous study, we carried out a genome-wide
association study using patients with PD and control individuals from
the isolated population of the Faroe Islands and identified chromosome
19p13.2 as a candidate region. To further investigate this chromosomal
region for association with PD, we analysed eight single nucleotide
polymorphisms (SNPs) in three candidate genes - small-nuclear RNA
activating complex, polypeptide 2 (SNAPC2), mitogen-activated protein
kinase kinase 7 (MAP2K7) and leucine-rich repeat containing 8 family,
member E (LRRC8E) - these genes have previously been directly or
indirectly implicated in other mental disorders. A total of 511 patients
with PD and 1029 healthy control individuals from the Faroe Islands,
Denmark and Germany were included in the current study. SNPs covering
the gene region of SNAPC2, MAP2K7 and LRRC8E were genotyped and tested
for association with PD. In the Faroese cohort, rs7788 within SNAPC2 was
significantly associated with PD, whereas rs3745383 within LRRC8E was
nominally associated. No association was observed between the analysed
SNPs and PD in the Danish cohorts. In the German women, we observed a
nominal association between rs4804833 within MAP2K7 and PD. We present
further evidence that chromosome 19p13.2 may harbour candidate genes
that contribute towards the risk of developing PD. Moreover, the
implication of the associated genes in other mental disorders may
indicate shared genetic susceptibility between mental disorders. We show
that associated variants may be sex specific, indicating the importance
of carrying out a sex-specific association analysis of PD. Copyright (C)
2016 Wolters Kluwer Health, Inc. All rights reserved.
