Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder View Full Text


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Article Info

DATE

2018-02-02

AUTHORS

Yoshiro Morimoto, Mihoko Shimada-Sugimoto, Takeshi Otowa, Shintaro Yoshida, Akira Kinoshita, Hiroyuki Mishima, Naohiro Yamaguchi, Takatoshi Mori, Akira Imamura, Hiroki Ozawa, Naohiro Kurotaki, Christiane Ziegler, Katharina Domschke, Jürgen Deckert, Tadashi Umekage, Mamoru Tochigi, Hisanobu Kaiya, Yuji Okazaki, Katsushi Tokunaga, Tsukasa Sasaki, Koh-ichiro Yoshiura, Shinji Ono

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. More... »

PAGES

41

References to SciGraph publications

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  • Journal

    TITLE

    Translational Psychiatry

    ISSUE

    1

    VOLUME

    8

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41398-017-0088-0

    DOI

    http://dx.doi.org/10.1038/s41398-017-0088-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100742484

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29391400


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