Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes

Kazutaka Ohi; Takeshi Otowa; Mihoko Shimada; Shunsuke Sugiyama; Yukimasa Muto; Shunsuke Tanahashi; Hisanobu Kaiya; Fumichika Nishimura; Tsukasa Sasaki; Hisashi Tanii; Toshiki Shioiri

doi:10.1016/j.euroneuro.2020.11.003

Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes

Eur Neuropsychopharmacol. 2021 Jan:42:87-96. doi: 10.1016/j.euroneuro.2020.11.003. Epub 2020 Nov 11.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, Gifu University Graduate School of Medicine, Gifu, Japan; Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan. Electronic address: k_ohi@gifu-u.ac.jp.
² Department of Neuropsychiatry, NTT Medical Center Tokyo, Tokyo, Japan.
³ Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo Japan.
⁴ Department of Psychiatry and Psychotherapy, Gifu University Graduate School of Medicine, Gifu, Japan.
⁵ Graduate School of Medicine, Department of Psychiatry, Mie University, Mie, Japan.
⁶ Panic Disorder Research Center, Warakukai Medical Corporation, Tokyo, Japan.
⁷ Center for Research on Counseling and Support Services, The University of Tokyo, Tokyo, Japan.
⁸ Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
⁹ Center for Physical and Mental Health, Mie University, Mie, Japan; Graduate School of Medicine, Department of Health Promotion and Disease Prevention, Mie University, Mie, Japan.

PMID: 33189524
DOI: 10.1016/j.euroneuro.2020.11.003

Abstract

Panic disorder (PD), a common anxiety disorder, is modestly heritable. The genetic basis of anxiety disorders overlaps with that of other psychiatric disorders and their intermediate phenotypes in individuals of European ancestry. Here, we investigated the transethnic polygenetic features shared between Japanese PD patients and European patients with psychiatric disorders and their intermediate phenotypes by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 7,556-1,131,881) for ten psychiatric disorders and seven intermediate phenotypes were utilized as discovery samples. PRSs derived from these GWASs were calculated for Japanese target subjects [718 PD patients and 1,717 healthy controls (HCs)]. The effects of these PRSs from European GWASs on the risk of PD in Japanese patients were investigated. The PRSs from European studies of anxiety disorders were marginally higher in Japanese PD patients than in HCs (p = 0.013). Regarding other psychiatric disorders, the PRSs for depression in European patients were significantly higher in Japanese PD patients than in HCs (p = 2.31×10^-4), while the PRSs for attention-deficit/hyperactivity disorder in European patients were nominally lower in Japanese PD patients than in HCs (p = 0.024). Regarding health-related, personality-based and cognitive intermediate phenotypes, the PRSs for loneliness (especially isolation) in European individuals were significantly higher in Japanese PD patients than in HCs (p = 9.02×10^-4). Furthermore, Japanese PD patients scored nominally higher than HCs in PRSs for neuroticism in European people (p = 3.37×10^-3), while Japanese PD patients scored nominally lower than HCs in PRSs for tiredness (p = 0.025), educational attainment (p = 0.035) and cognitive function (p = 9.63×10^-3). Our findings suggest that PD shares transethnic genetic etiologies with other psychiatric disorders and related intermediate phenotypes.

Keywords: Anxiety disorder; Depression; Intermediate phenotype; Loneliness; Panic disorder; Polygenic risk score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Depressive Disorder, Major*
Genome-Wide Association Study
Humans
Multifactorial Inheritance
Panic Disorder* / genetics
Phenotype