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Inhibitory neuron links the causal relationship from air pollution to psychiatric disorders: a large multi-omics analysis

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机构: [1]Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China [2]Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha 410008, Hunan, Peoples R China [3]Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China [4]Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China [5]Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing 400010, Peoples R China [6]Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou 510000, Guangdong, Peoples R China [7]Kunming Med Univ, Affiliated Hosp 1, Dept Neurosurg, Kunming 650032, Yunnan, Peoples R China
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关键词: Psychiatric disorders PM2 5 NO2 Mendelian randomization Single-cell RNA analyses

摘要:
Psychiatric disorders are severe health challenges that exert a heavy public burden. Air pollution has been widely reported as related to psychiatric disorder risk, but their casual association and pathological mechanism remained unclear. Herein, we systematically investigated the large genome-wide association studies (6 cohorts with 1,357,645 samples), single-cell RNA (26 samples with 157,488 cells), and bulk-RNAseq (1595 samples) datasets to reveal the genetic causality and biological link between four air pollutants and nine psychiatric disorders. As a result, we identified ten positive genetic correlations between air pollution and psychiatric disorders. Besides, PM2.5 and NO2 presented significant causal effects on schizophrenia risk which was robust with adjustment of potential confounders. Besides, transcriptome-wide association studies identified the shared genes between PM2.5/NO2 and schizophrenia. We then discovered a schizophrenia-derived inhibitory neuron subtype with highly expressed shared genes and abnormal synaptic and metabolic pathways by scRNA analyses and confirmed their abnormal level and correlations with the shared genes in schizophrenia patients in a large RNA-seq cohort. Comprehensively, we discovered robust genetic causality between PM2.5, NO2, and schizophrenia and identified an abnormal inhibitory neuron subtype that links schizophrenia pathology and PM2.5/NO2 exposure. These discoveries highlight the schizophrenia risk under air pollutants exposure and provide novel mechanical insights into schizophrenia pathology, contributing to pollutant-related schizophrenia risk control and therapeutic strategies development.

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大类 | 2 区 计算机科学
小类 | 2 区 计算机:理论方法
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Q1 COMPUTER SCIENCE, THEORY & METHODS

影响因子: 最新[2023版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2023版]

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第一作者机构: [1]Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China [2]Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha 410008, Hunan, Peoples R China [3]Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
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通讯机构: [1]Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China [2]Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha 410008, Hunan, Peoples R China [3]Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
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