Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes.
Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes.
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恐慌症和精神病学及相关中间表型具有共同的跨种族遗传基础。
DOI：
10.1016/j.euroneuro.2020.11.003
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Shioiri T
中科院分区：
文献类型：
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作者：
Ohi K;Otowa T;Shimada M;Sugiyama S;Muto Y;Tanahashi S;Kaiya H;Nishimura F;Sasaki T;Tanii H;Shioiri T
恐慌症(PD)是一种常见的焦虑症，具有一定的遗传性。焦虑症的遗传基础与其他精神障碍及其在欧洲血统个体中的中间表型重叠。在这里，我们通过进行多基因风险评分(PRS)分析，研究了日本帕金森病患者和欧洲精神障碍患者之间共有的跨性多基因特征及其中间表型。10种精神疾病和7种中间表型的大规模欧洲基因组范围关联研究(GWAS)数据集(n=77,556-1,131,881)被用作发现样本。从这些GWAS得出的PRSS被计算为日本目标受试者[718名PD患者和1717名健康对照(HCS)]。研究了来自欧洲GWAS的这些PRS对日本患者帕金森病风险的影响。来自欧洲焦虑症研究的日本PD患者的PRSS略高于HCS患者(p=0.013)。在其他精神障碍方面，日本帕金森病患者中，欧洲患者抑郁症的PRSS显著高于欧洲帕金森病患者(p=2.31×10-4)，而日本帕金森病患者的注意力缺陷/多动障碍的PRSS名义上低于HCS患者(p=0.024)。在与健康相关的、基于个性的和认知中间表型方面，欧洲人孤独(尤其是隔离)的PRSS在日本PD患者中显著高于HCS患者(p=39.02×10-4)。此外，在欧洲人中，日本PD患者在PRSS中神经质的得分高于HCS(p=3.37×10-3)，而在疲倦(p=0.0.025)、教育程度(p=0.035)和认知功能(p=9.63×10-3)方面，日本PD患者在PRSS中的得分低于HCS。我们的发现表明，帕金森病与其他精神障碍和相关的中间表型具有相同的跨性遗传病因。
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.