Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer
Abstract Background Alzheimer’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. Methods Based on genome-wide associa...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04357-3 |
| _version_ | 1797556844910084096 |
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| author | Zehua Dong Mengli Xu Xu Sun Xiaosheng Wang |
| author_facet | Zehua Dong Mengli Xu Xu Sun Xiaosheng Wang |
| author_sort | Zehua Dong |
| collection | DOAJ |
| description | Abstract Background Alzheimer’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. Methods Based 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. Results Two-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. Conclusion AD 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. |
| first_indexed | 2024-03-10T17:07:47Z |
| format | Article |
| id | doaj.art-51f76088f9bc4f8397524ccbef142814 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-10T17:07:47Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-51f76088f9bc4f8397524ccbef1428142023-11-20T10:44:38ZengBMCJournal of Translational Medicine1479-58762023-08-0121111010.1186/s12967-023-04357-3Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancerZehua Dong0Mengli Xu1Xu Sun2Xiaosheng Wang3Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversityBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversityDepartment of Pharmacy, Nanjing Luhe People’s HospitalBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversityAbstract Background Alzheimer’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. Methods Based 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. Results Two-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. Conclusion AD 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.https://doi.org/10.1186/s12967-023-04357-3Alzheimer’s diseaseCancerMendelian randomizationColocalization analysisTranscriptome analysis |
| spellingShingle | Zehua Dong Mengli Xu Xu Sun Xiaosheng Wang Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer Journal of Translational Medicine Alzheimer’s disease Cancer Mendelian randomization Colocalization analysis Transcriptome analysis |
| title | Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer |
| title_full | Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer |
| title_fullStr | Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer |
| title_full_unstemmed | Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer |
| title_short | Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer |
| title_sort | mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between alzheimer s disease and cancer |
| topic | Alzheimer’s disease Cancer Mendelian randomization Colocalization analysis Transcriptome analysis |
| url | https://doi.org/10.1186/s12967-023-04357-3 |
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