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Identification of JAZF1, KNOP1, and PLEKHA1 as causally associated genes and drug targets for Alzheimer's disease: a summary data-based Mendelian randomization study

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机构: [1]Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China [2]Department of Cardiac Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China [3]Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China [4]Department of Neurology, Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China [5]Faculty of Health Science, University of Macau, Taipa, Macao SAR, China [6]Center for Primary Health Care Research, Department of Clinical Sciences Malm., Lund University, Malm., Sweden [7]Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
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关键词: Alzheimer’s disease Immune cells Summary-data-based Mendelian randomization Causal association

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There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic, colocalization, and assessment of horizontal pleiotropy, were further conducted to validate the discovered genes. In addition, replication analyses were performed in AD GWAS from the FinnGen consortium. Finally, we further identified existing drugs that target or interact with the druggable genes and reviewed the studies about the associations between these drugs and AD.SMR analysis revealed 342 genes associated with AD across 14 immune cell types. Further sensitivity analyses identified nine genes, CTSH, FCER1G, FNBP4, HLA-E, JAZF1, KNOP1, PLEKHA1, RP11-960L18.1, and ZNF638 that had significant associations with AD across nine specific immune cell types. JAZF1, KNOP1 and PLEKHA1 were replicated in an independent analysis using the GWAS data. The review on gene-related drugs also supported these findings.Our research suggests that the expression of the genes JAZF1, KNOP1, and PLEKHA1 in specific immune cell types is related to the risk of AD.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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大类 | 2 区 医学
小类 | 1 区 毒理学 3 区 免疫学
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 毒理学 3 区 免疫学
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Q1 TOXICOLOGY Q2 IMMUNOLOGY
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Q1 TOXICOLOGY Q2 IMMUNOLOGY

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第一作者机构: [1]Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
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通讯机构: [1]Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China [5]Faculty of Health Science, University of Macau, Taipa, Macao SAR, China [6]Center for Primary Health Care Research, Department of Clinical Sciences Malm., Lund University, Malm., Sweden [7]Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
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