TY  - JOUR
A1  - Morimoto, Yoshiro
A1  - Shimada-Sugimoto, Mihoko
A1  - Otowa, Takeshi
A1  - Yoshida, Shintaro
A1  - Kinoshita, Akira
A1  - Mishima, Hiroyuki
A1  - Yamaguchi, Naohiro
A1  - Mori, Takatoshi
A1  - Imamura, Akira
A1  - Ozawa, Hiroki
A1  - Kurotaki, Naohiro
A1  - Ziegler, Christiane
A1  - Domschke, Katharina
A1  - Deckert, Jürgen
A1  - Umekage, Tadashi
A1  - Tochigi, Mamoru
A1  - Kaiya, Hisanobu
A1  - Okazaki, Yuji
A1  - Tokunaga, Katsushi
A1  - Sasaki, Tsukasa
A1  - Yoshiura, Koh-ichiro
A1  - Ono, Shinji
T1  - Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder
JF  - Translational Psychiatry
N2  - 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.
KW  - clinical genetics
KW  - medical genetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224192
VL  - 8
ER  -