Year of grant:
Heilsa - Sjúkrakassagrunnurin
Identifying and analysing genetic risk variants for panic disorder in the isolated population of the Faroe Islands
Noomi Oddmarsdóttir Gregersen
Ole Mors, Anders Børglum, Henriette Nørmølle Buttenschøn, Ditte Demontis og August G. Wang
Grant from the FRC in DKK:
Panic disorder (PD) is a mental disorder characterized by recurrent and unprovoked panic attacks, which untreated will result in substantial distress and impairment. Patients suffering from PD have an increased risk of coHmorbid psychosis, bipolar disorder, substance abuse, depression, and suicide. Despite the high heritability of PD only a few genes have been identified as risk genes for PD. Now we have the unique opportunity to analyse wholeHexome sequencing data conducted on patients with PD and control individuals from the Faroe Islands.
The aim of the present project is to perform additional data mining of the already generated wholeHexome sequencing data in order to evaluate further the genetic architecture of PD. The here proposed project focuses on variants in nonH coding regions, in order to give a more complete picture of the genetic risk components of PD on the Faroe Islands. By imputing using offHtarget sequencing reads from the exome data we expect to capture most of the common variation of the wholeHgenome, which may lead to identification of specific biological pathways involved in PD. This project will contribute to the present knowledge and understanding of the genetic architecture of PD.
Identifying genetic risk factors for PD is the first step towards elucidating the biological disease mechanisms involved in the aetiology of this disorder and will enable targeted approaches for disease treatment, and ideally also prevention.
Identifying genetic risk factors for panic disorder (PD) is the first step towards elucidating the biological disease mechanisms involved in the aetiology of the disorder, and may eventual lead improved treatment or prevention of PD. In this project we analysed whole-exome data from 54 patients with PD and 211 healty controls, all individuals from the Faroe Islands. The aim was to identify genetic risk variants contributing to the developing of PD. Interestingly, the most associated gene was DGKH, which is one of the most replicated candidate genes for bipolar disorder. These results suggest that DGKH may be a cross-disorder risk gene, and that PD should be included in future cross-disorders mega-analysis. Furthermore, we looked for enrichment of rare variants in the Faroese population. We observed a separate clustering of the Faroese individuals compared to other European populations included in the 1000 Genome Populations, and also observed an enrichment of otherwise rare or previously unobserved variants. This finding supports the use of the Faroese population in identifying rare risk variants contributing to the development of PD. Overall this project contributes to the present knowledge and understanding of the genetic architecture of PD. The work was been publiced in a peer review journal
Gregersen et al. 2016: Whole-Exome Sequencing Implicates DGKH as a Risk Gene for Panic Disorder in the Faroese Population. Am J Med Genet B Neuropsychiatr Genet. 171:1013-1022