1. Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder
- Author
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Tsukasa Sasaki, Tadashi Umekage, Hiroki Ozawa, Takeshi Otowa, Katharina Domschke, Mamoru Tochigi, Hisanobu Kaiya, Shintaro Yoshida, Koh-ichiro Yoshiura, Jürgen Deckert, Takatoshi Mori, Yoshiro Morimoto, Akira Imamura, Naohiro Kurotaki, Akira Kinoshita, Shinji Ono, Mihoko Shimada-Sugimoto, Christiane Ziegler, Katsushi Tokunaga, Naohiro Yamaguchi, Hiroyuki Mishima, and Yuji Okazaki
- Subjects
0301 basic medicine ,Adult ,Male ,Risk ,medicine.medical_specialty ,Rare variant association ,Article ,lcsh:RC321-571 ,Pathogenesis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Japan ,Germany ,Epidemiology ,Exome Sequencing ,medicine ,Humans ,Gene ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,Exome sequencing ,Genetic Association Studies ,Genetics ,business.industry ,Panic disorder ,Group IV Phospholipases A2 ,Case-control study ,Panic ,medicine.disease ,Pedigree ,Psychiatry and Mental health ,030104 developmental biology ,Case-Control Studies ,Panic Disorder ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case–control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case–control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.
- Published
- 2018