Evidence map›Paper›PMID 37542274›Full record

ArticleJournal of translational medicine2023

Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer's disease and cancer.

Zehua Dong, Mengli Xu, Xu Sun, Xiaosheng Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Zehua DongBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Mengli XuBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Xu SunDepartment of Pharmacy, Nanjing Luhe People's Hospital, Nanjing, 211500, China. sunxu@njslhormyy2.wecom.work.
Xiaosheng WangBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. xiaosheng.wang@cpu.edu.cn.ORCID http://orcid.org/0000-0002-7199-7093
China Pharmaceutical University · CNNanjing Traditional Chinese Medicine Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) and cancer are common age-related diseases, and epidemiological evidence suggests an inverse relationship between them. However, investigating the potential mechanism underlying their relationship remains insufficient.

methodsBased on genome-wide association summary statistics for 42,034 AD patients and 609,951 cancer patients from the GWAS Catalog using the two-sample Mendelian randomization (MR) method. Moreover, we utilized two-step MR to identify metabolites mediating between AD and cancer. Furthermore, we employed colocalization analysis to identify genes whose upregulation is a risk factor for AD and demonstrated the genes' upregulation to be a favorable prognostic factor for cancer by analyzing transcriptomic data for 33 TCGA cancer types.

resultsTwo-sample MR analysis revealed a significant causal influence for increased AD risk on reduced cancer risk. Two-step MR analysis identified very low-density lipoprotein (VLDL) as a key mediator of the negative cause-effect relationship between AD and cancer. Colocalization analysis uncovered PVRIG upregulation to be a risk factor for AD. Transcriptomic analysis showed that PVRIG expression had significant negative correlations with stemness scores, and positive correlations with antitumor immune responses and overall survival in pan-cancer and multiple cancer types.

conclusionAD may result in lower cancer risk. VLDL is a significant intermediate variable linking AD with cancer. PVRIG abundance is a risk factor for AD but a protective factor for cancer. This study demonstrates a causal influence for AD on cancer and provides potential molecular connections between both diseases.

Indexed as

Alzheimer DiseaseNeoplasmsGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideTranscriptomeAlzheimer’s diseaseCancerColocalization analysisMendelian randomizationTranscriptome analysis

Identifiers

PMID37542274
PMCPMC10403895
OpenAlexW4385577594

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.