title: Chromosome 4q31-34 panic disorder risk locus: association of neuropeptide Y Y5 receptor variants.
abstract: There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with a recent linkage study pointing toward a risk locus on chromosome 4q31-q34 [Kaabi et al., 2006]. Since the neuropeptide Y (NPY) system has been reported to be involved in the pathophysiology of anxiety and in particular panic disorder and the genes coding for NPY Y1, Y2, and Y5 receptors are located in the suggested risk region (4q31-q32), variants in the NPY, NPY Y1, Y2, and Y5 genes were investigated for association with panic disorder in a sample of 230 German patients with panic disorder and matched healthy controls. A synonymous (Gly-426-Gly) NPY Y5 coding variant (rs11946004) as well as haplotypes including rs11946004 and an intronic NPY Y5 variant (rs11724320) were significantly associated with panic disorder (P = 0.027), with the effect originating from the subgroup of female patients (P = 0.030), particularly with concurrent agoraphobia (P = 0.002-0.019). No association was observed for any variants located in the genes coding for NPY, NPY Y1, or Y2. The present results provide preliminary support for an influence of NPY Y5 receptor variants on the etiology of panic disorder in a potentially gender-specific manner further strengthening the evidence for a risk locus on chromosome 4q31-q34 in anxiety disorders. However, in order to allow for conclusive evaluation of the present finding and to exclude a false positive result, further studies in larger, independent, preferably family based samples are warranted.
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany. katharina.domschke@ukmuenster.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Christa
authors.initials: C
authors.lastname: Hohoff
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Jürgen
authors.initials: J
authors.lastname: Fritze
authors.forename: Borwin
authors.initials: B
authors.lastname: Bandelow
authors.forename: Petra
authors.initials: P
authors.lastname: Krakowitzky
authors.forename: Florian
authors.initials: F
authors.lastname: Kästner
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
mesh_terms: D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4; D005260:Female; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D005810:Multigene Family; D016584:Panic Disorder / Q000235:genetics*; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D012737:Sex Factors
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor