通过计算生物学量化阿尔茨海默病的个性化转变工作分子特征

Y. Xu, G. Zhang, L. Yang, H. Qin, Z. Zhou, Q. Li, H. Liu, R. Wang, Z. Cai, L. Jing, Y. Li, Y. Yao, Z. Gong, P. Yuan, T. Fu, X. Zhao, Tao Peng, Yanjie Jia
{"title":"通过计算生物学量化阿尔茨海默病的个性化转变工作分子特征","authors":"Y. Xu, G. Zhang, L. Yang, H. Qin, Z. Zhou, Q. Li, H. Liu, R. Wang, Z. Cai, L. Jing, Y. Li, Y. Yao, Z. Gong, P. Yuan, T. Fu, X. Zhao, Tao Peng, Yanjie Jia","doi":"10.14283/jpad.2024.161","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Shift work, the proven circadian rhythm-disrupting behavior, has been linked to the increased risk of Alzheimer’s disease (AD). However, the putative causal effect and potential mechanisms of shift work for AD were still unclear.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Mendelian randomization (MR) analysis was performed to discover the putative causal effect of shift work for AD. Expression quantitative trait loci (eQTLs) and transcriptome data were integrated to identify genes causally associated with AD from circadian-related genes. An in vitro experiment was also conducted to validate the expression of target genes. Based on the identified genes, a novel integrative program and 4,077 samples from 16 microarray datasets were leveraged to assess the extent of circadian rhythm disruption (CRD), defined as the clock deviation level (CDL).</p><h3 data-test=\"abstract-sub-heading\">Findings/Results</h3><p>Shift work causally increased the risk of AD [odds ratio (OR) = 2.49, 95% CI = 1.79 - 3.19, p = 0.01]. Seven circadian-related genes were causally associated with AD, including CCS, CDS2, MYRIP, NRP1, PLEKHA5, POLR1D, and PPP4C. These genes were significantly correlated with the circadian rhythm pathway. CDL was higher in CRD mice group, shift work group, sleep restriction group, and AD patients compared to control mice group (p = 0.043), non-shift group (p = 0.004), sleep extension group (p = 0.025), and health controls (multiple cohorts, p &lt; 0.05). Additionally, CDL was also significantly correlated with AD’s clinical biomarkers.</p><h3 data-test=\"abstract-sub-heading\">Interpretations/Conclusion</h3><p>By combining GWAS and transcriptome data, this study demonstrated the causal role of CRD behavior in AD, identified the potential target genes in shift work-induced AD, and generated CDL to characterize CRD status, which provided evidence and prospects for disease prevention and future therapeutic interventions.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"9 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantifying Personalized Shift-Work Molecular Portraits Underlying Alzheimer’s Disease through Computational Biology\",\"authors\":\"Y. Xu, G. Zhang, L. Yang, H. Qin, Z. Zhou, Q. Li, H. Liu, R. Wang, Z. Cai, L. Jing, Y. Li, Y. Yao, Z. Gong, P. Yuan, T. Fu, X. Zhao, Tao Peng, Yanjie Jia\",\"doi\":\"10.14283/jpad.2024.161\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Shift work, the proven circadian rhythm-disrupting behavior, has been linked to the increased risk of Alzheimer’s disease (AD). However, the putative causal effect and potential mechanisms of shift work for AD were still unclear.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Mendelian randomization (MR) analysis was performed to discover the putative causal effect of shift work for AD. Expression quantitative trait loci (eQTLs) and transcriptome data were integrated to identify genes causally associated with AD from circadian-related genes. An in vitro experiment was also conducted to validate the expression of target genes. Based on the identified genes, a novel integrative program and 4,077 samples from 16 microarray datasets were leveraged to assess the extent of circadian rhythm disruption (CRD), defined as the clock deviation level (CDL).</p><h3 data-test=\\\"abstract-sub-heading\\\">Findings/Results</h3><p>Shift work causally increased the risk of AD [odds ratio (OR) = 2.49, 95% CI = 1.79 - 3.19, p = 0.01]. Seven circadian-related genes were causally associated with AD, including CCS, CDS2, MYRIP, NRP1, PLEKHA5, POLR1D, and PPP4C. These genes were significantly correlated with the circadian rhythm pathway. CDL was higher in CRD mice group, shift work group, sleep restriction group, and AD patients compared to control mice group (p = 0.043), non-shift group (p = 0.004), sleep extension group (p = 0.025), and health controls (multiple cohorts, p &lt; 0.05). Additionally, CDL was also significantly correlated with AD’s clinical biomarkers.</p><h3 data-test=\\\"abstract-sub-heading\\\">Interpretations/Conclusion</h3><p>By combining GWAS and transcriptome data, this study demonstrated the causal role of CRD behavior in AD, identified the potential target genes in shift work-induced AD, and generated CDL to characterize CRD status, which provided evidence and prospects for disease prevention and future therapeutic interventions.</p>\",\"PeriodicalId\":22711,\"journal\":{\"name\":\"The Journal of Prevention of Alzheimer's Disease\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Prevention of Alzheimer's Disease\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14283/jpad.2024.161\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BUSINESS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Prevention of Alzheimer's Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14283/jpad.2024.161","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BUSINESS","Score":null,"Total":0}
引用次数: 0

摘要

背景轮班工作是已被证实会破坏昼夜节律的行为,它与阿尔茨海默病(AD)患病风险的增加有关。然而,轮班工作对阿尔茨海默病的假定因果效应和潜在机制仍不清楚。方法为了发现轮班工作对阿尔茨海默病的假定因果效应,研究人员进行了孟德尔随机化(MR)分析。通过整合表达定量性状位点(eQTLs)和转录组数据,从昼夜节律相关基因中找出与AD有因果关系的基因。同时还进行了体外实验来验证目标基因的表达。根据确定的基因,利用新的整合程序和来自 16 个微阵列数据集的 4,077 个样本来评估昼夜节律紊乱(CRD)的程度,即时钟偏差水平(CDL)。7个昼夜节律相关基因与AD存在因果关系,包括CCS、CDS2、MYRIP、NRP1、PLEKHA5、POLR1D和PPP4C。这些基因与昼夜节律途径明显相关。与对照小鼠组(p = 0.043)、非轮班组(p = 0.004)、睡眠延长组(p = 0.025)和健康对照组(多个队列,p <0.05)相比,CRD小鼠组、轮班工作组、睡眠限制组和AD患者的CDL更高。此外,CDL还与AD的临床生物标志物显著相关。解释/结论本研究通过结合GWAS和转录组数据,证明了CRD行为在AD中的因果作用,确定了轮班工作诱发AD的潜在靶基因,并生成了表征CRD状态的CDL,为疾病预防和未来的治疗干预提供了证据和前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Quantifying Personalized Shift-Work Molecular Portraits Underlying Alzheimer’s Disease through Computational Biology

Background

Shift work, the proven circadian rhythm-disrupting behavior, has been linked to the increased risk of Alzheimer’s disease (AD). However, the putative causal effect and potential mechanisms of shift work for AD were still unclear.

Methods

Mendelian randomization (MR) analysis was performed to discover the putative causal effect of shift work for AD. Expression quantitative trait loci (eQTLs) and transcriptome data were integrated to identify genes causally associated with AD from circadian-related genes. An in vitro experiment was also conducted to validate the expression of target genes. Based on the identified genes, a novel integrative program and 4,077 samples from 16 microarray datasets were leveraged to assess the extent of circadian rhythm disruption (CRD), defined as the clock deviation level (CDL).

Findings/Results

Shift work causally increased the risk of AD [odds ratio (OR) = 2.49, 95% CI = 1.79 - 3.19, p = 0.01]. Seven circadian-related genes were causally associated with AD, including CCS, CDS2, MYRIP, NRP1, PLEKHA5, POLR1D, and PPP4C. These genes were significantly correlated with the circadian rhythm pathway. CDL was higher in CRD mice group, shift work group, sleep restriction group, and AD patients compared to control mice group (p = 0.043), non-shift group (p = 0.004), sleep extension group (p = 0.025), and health controls (multiple cohorts, p < 0.05). Additionally, CDL was also significantly correlated with AD’s clinical biomarkers.

Interpretations/Conclusion

By combining GWAS and transcriptome data, this study demonstrated the causal role of CRD behavior in AD, identified the potential target genes in shift work-induced AD, and generated CDL to characterize CRD status, which provided evidence and prospects for disease prevention and future therapeutic interventions.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
CiteScore
9.20
自引率
0.00%
发文量
0
期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
期刊最新文献
Association between Cognitive Reserve Indicator and Chronic Disease-Free Survival: A Large Community-Based Longitudinal Study Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer’s Disease Roles of TREM2 in the Pathological Mechanism and the Therapeutic Strategies of Alzheimer’s Disease Development and Validation the Mobile Toolbox (MTB) Spelling Test Correlates of Subjective Cognitive Decline in Black American Men
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1