[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.目的： 探讨多基因风险评分（PRS）和肠道真菌的交互作用对精神分裂症（SCH）发病的影响。 方法： 本研究为病例对照研究，回顾性选取2017年10月至2019年10月就诊于郑州大学第一附属医院精神科的首发未用药SCH患者作为病例组，选取经过广告招募及来医院体检的健康人群作为对照组。采用18S 核糖体RNA（rRNA）测序平台检测肠道真菌水平。通过logistic回归模型探讨肠道真菌失调（F_MD）指数、α多样性指数和PRS与SCH发病风险的关系。连续变量间的相关分析采用偏相关分析，相关（P<0.05）的变量纳入回归模型，采用线性回归分析多个自变量和因变量之间的关系。 结果： 本研究共纳入了137例首发未用药SCH患者（男62例，女75例）和76名健康对照者（男31名，女45名）。患者组年龄为（22.5±7.5）岁，对照组年龄为（22.8±2.3）岁。PRS评分升高是SCH发病的危险因素（OR=1.111，95%CI：1.036~1.178，P=0.002）。F_MD指数升高是SCH发病的危险因素（OR=1.200，95%CI：1.124~1.281，P<0.001）。真菌α多样性Shannon指数（OR=0.813，95%CI：0.755~0.874，P<0.001）和Simpson指数（OR=0.218，95%CI：0.091~0.523，P<0.001）升高是SCH发病的保护因素。关键菌曲霉菌属丰度升高是SCH发病的保护因素（OR=0.928，95%CI：0.864~0.996，P=0.040）。曲霉菌属丰度和认知功能领域中的工作记忆（r=0.280，P=0.001），词语学习（r=0.253，P=0.003）、推理和问题解决（r=0.191，P=0.028）呈正相关。 结论： PRS升高是SCH发病的风险因素，肠道真菌α多样性指数升高和曲霉菌属丰度升高可能是SCH的保护因素，PRS与肠道真菌（Shannon指数、Simpson指数和曲霉菌属）交互作用是SCH发病的相关因素。.