Mendelian randomization and transcriptomic analysis reveal a positive cause-and-effect relationship between Alzheimer's disease and colorectal cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-27 DOI:10.1016/j.tranon.2024.102169

Wei Du , Xueming Xia , Qiheng Gou , Yan Qiu

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引用次数: 0

Abstract

Background

This study addresses the complex multifactorial causes of Alzheimer's disease (AD) and colorectal cancer (CRC), two significant public health issues. Despite previous research, the precise relationship between AD and CRC remains unclear. This study aimed to explore the potential causal relationship between AD and CRC using Mendelian randomization (MR) and to identify risk genes through colocalization and transcriptomic analyses.

Method

The study used a two-sample Mendelian randomization (MR) approach to investigate the causal effect of AD on CRC. Genome-wide association study (GWAS) summary statistics for AD and CRC were utilized. Colocalization analysis was conducted to identify risk genes associated with AD, which were then validated through transcriptomic analysis in CRC samples. The study used GWAS data from a cohort of European patients and applied several MR methods, including MR Egger, weighted median, and inverse-variance weighted approaches, to ensure robust findings.

Results

The MR analysis revealed a significant positive causal relationship between AD and CRC, indicating that an increased genetic predisposition to AD is associated with a elevated risk of developing CRC. The colocalization analysis identified COLEC11 as a significant risk gene for AD, which also showed a strong positive correlation with clinical features and survival outcomes in CRC. Elevated COLEC11 expression was linked to advanced clinical stages, increased tumor mutational burden, microsatellite instability, and poorer overall survival in CRC patients.

Conclusions

This study provides evidence of a causal relationship between AD and CRC, suggesting that shared genetic and inflammatory pathways may underlie both conditions. The identification of COLEC11 as a potential link between AD and CRC offers new avenues for research and therapeutic interventions. These findings contribute to a deeper understanding of the interplay between neurodegenerative and oncologic diseases, highlighting the importance of exploring common pathogenic mechanisms.

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孟德尔随机化和转录组分析揭示了阿尔茨海默病与结直肠癌之间的正向因果关系

背景本研究探讨了阿尔茨海默病（AD）和结肠直肠癌（CRC）这两个重大公共卫生问题的复杂多因素成因。尽管此前已有研究，但阿尔茨海默病和结肠直肠癌之间的确切关系仍不清楚。本研究旨在利用孟德尔随机法（Mendelian randomization，MR）探讨AD与CRC之间的潜在因果关系，并通过共定位和转录组分析确定风险基因。研究利用了AD和CRC的全基因组关联研究（GWAS）摘要统计。通过共定位分析确定了与 AD 相关的风险基因，然后通过对 CRC 样本进行转录组分析验证了这些基因。该研究使用了来自欧洲患者队列的 GWAS 数据，并应用了多种 MR 方法，包括 MR Egger、加权中位数和逆方差加权方法，以确保研究结果的稳健性。结果MR 分析显示，AD 和 CRC 之间存在显著的正因果关系，表明 AD 遗传易感性的增加与 CRC 患病风险的升高有关。共定位分析发现 COLEC11 是 AD 的一个重要风险基因，该基因与 CRC 的临床特征和生存结果也有很强的正相关性。COLEC11表达的升高与CRC患者的临床分期、肿瘤突变负荷增加、微卫星不稳定性和总生存率较低有关。将 COLEC11 鉴定为 AD 和 CRC 之间的潜在联系为研究和治疗干预提供了新途径。这些发现有助于加深对神经退行性疾病和肿瘤疾病之间相互作用的理解，突出了探索共同致病机制的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.