Department of Psychiatry and Psychotherapy, Gifu University Graduate School of Medicine, Gifu, Japan; Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Department of Neuropsychiatry, NTT Medical Center Tokyo, Tokyo, Japan.
Eur Neuropsychopharmacol. 2021 Jan;42:87-96. doi: 10.1016/j.euroneuro.2020.11.003. Epub 2020 Nov 11.
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), 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). Furthermore, Japanese PD patients scored nominally higher than HCs in PRSs for neuroticism in European people (p = 3.37×10), 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). Our findings suggest that PD shares transethnic genetic etiologies with other psychiatric disorders and related intermediate phenotypes.
惊恐障碍（PD）是一种常见的焦虑障碍，其具有一定的遗传性。焦虑障碍的遗传基础与欧洲血统个体的其他精神障碍及其中间表型重叠。在这里，我们通过进行多基因风险评分（PRS）分析，研究了日本 PD 患者与欧洲精神障碍患者及其中间表型之间的跨种族多基因特征。利用来自欧洲的大规模全基因组关联研究（GWAS）数据集（n=7556-1131881）对十种精神障碍和七种中间表型进行了分析。从这些 GWAS 中得出的 PRS 被计算出来，并应用于日本目标人群[718 名 PD 患者和 1717 名健康对照（HC）]。研究了这些欧洲 GWAS 的 PRS 对日本 PD 患者患病风险的影响。来自欧洲焦虑障碍研究的 PRS 在日本 PD 患者中略高于 HC（p=0.013）。关于其他精神障碍，欧洲患者的抑郁 PRS 在日本 PD 患者中明显高于 HC（p=2.31×10），而欧洲患者的注意缺陷/多动障碍 PRS 在日本 PD 患者中略低于 HC（p=0.024）。关于与健康相关的、基于人格的和认知的中间表型，欧洲个体的孤独（特别是孤立）PRS 在日本 PD 患者中明显高于 HC（p=9.02×10）。此外，日本 PD 患者的神经质 PRS 评分在欧洲人群中略高于 HC（p=3.37×10），而疲倦（p=0.025）、受教育程度（p=0.035）和认知功能（p=9.63×10）的 PRS 评分在日本 PD 患者中则略低于 HC。我们的研究结果表明，PD 与其他精神障碍及其相关中间表型具有跨种族的遗传病因。
