Association between genes on chromosome 19p13.2 and panic disorder.
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.
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.
Noomi O
NO
Gregersen
Henriette N
HN
Buttenschøn
Anne
A
Hedemand
Marit N
MN
Nielsen
Hans A
HA
Dahl
Ann S
AS
Kristensen
Oddbjørg
O
Johansen
David P D
DP
Woldbye
Angelika
A
Erhardt
Torben A
TA
Kruse
August G
AG
Wang
Anders D
AD
Børglum
Ole
O
Mors
D000328:Adult; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D048688:MAP Kinase Kinase 7 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D016584:Panic Disorder / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
C485976:LRRC8A protein, human; D008565:Membrane Proteins; C099437:SNAPC2 protein, human; D014157:Transcription Factors; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human