| Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease |
| Li, Y; Xu, M; Xiang, BL; Li, X ; Zhang, DF; Zhao, H; Bi, R; Yao, YG
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| 2023
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| 发表期刊 | NEUROPSYCHOPHARMACOLOGY
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| ISSN | 0893-133X
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| 卷号 | 48期号:11页码:1555-1566 |
| 摘要 | Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, which has a high heritability of up to 79%. Exploring the genetic basis is essential for understanding the pathogenic mechanisms underlying AD development. Recent genome-wide association studies (GWASs) reported an AD-associated signal in the Cathepsin H (CTSH) gene in European populations. However, the exact functional/causal variant(s), and the genetic regulating mechanism of CTSH in AD remain to be determined. In this study, we carried out a comprehensive study to characterize the role of CTSH variants in the pathogenesis of AD. We identified rs2289702 in CTSH as the most significant functional variant that is associated with a protective effect against AD. The genetic association between rs2289702 and AD was validated in independent cohorts of the Han Chinese population. The CTSH mRNA expression level was significantly increased in AD patients and AD animal models, and the protective allele T of rs2289702 was associated with a decreased expression level of CTSH through the disruption of the binding affinity of transcription factors. Human microglia cells with CTSH knockout showed a significantly increased phagocytosis of A beta peptides. Our study identified CTSH as being involved in AD genetic susceptibility and uncovered the genetic regulating mechanism of CTSH in pathogenesis of AD. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14035
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| 专题 | 科研部门_疾病机理遗传学和进化医学学科组（姚永刚）
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推荐引用方式
GB/T 7714 |
Li, Y,Xu, M,Xiang, BL,et al. Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease[J]. NEUROPSYCHOPHARMACOLOGY,2023,48(11):1555-1566.
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| APA |
Li, Y.,Xu, M.,Xiang, BL.,Li, X.,Zhang, DF.,...&Yao, YG.(2023).Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.NEUROPSYCHOPHARMACOLOGY,48(11),1555-1566.
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| MLA |
Li, Y,et al."Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease".NEUROPSYCHOPHARMACOLOGY 48.11(2023):1555-1566.
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