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Association between genes on chromosome 19p13.2 and panic disorder

Gregersen, Noomi O.; Buttenschøn, Henriette N.; Hedemand, Anne; Nielsen, Marit N.; Dahl, Hans A.; Kristensen, Ann S.; Johansen, Oddbjørg; Woldbye, David P.D.; Erhardt, Angelika; Kruse, Torben A.; Wang, August G.; Børglum, Anders D.; Mors, Ole

doi: 10.1097/YPG.0000000000000147

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.

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aTranslational Neuropsychiatry Unit, Department of Clinical Medicine

bDepartment of Biomedicine, Centre for Integrative Sequencing (iSEQ), Aarhus University

cThe Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus

dAmplexa Genetics A/S

eDepartment of Clinical Genetics, University of Southern Denmark, Odense

fPsychosis Research Unit, Aarhus University Hospital, Risskov

gLaboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen

hCentre of Psychiatry Amager, Copenhagen University Hospital, Copenhagen, Denmark

iDepartment of Psychiatry, The National Hospital, The Faroe Islands

jDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany

Correspondence to Noomi O. Gregersen, PhD, Translational Neuropsychiatry Unit, Department of Clinical Medicine, University of Aarhus, Skovagervej 2, DK-8240 Risskov, Denmark Tel: +45 298 233050; fax: +45 298 304705; e-mail:

Received September 30, 2015

Received in revised form May 19, 2016

Accepted July 19, 2016

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