Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study
Abstract Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and that lipid-lowering drugs may reduce the risk of PC. However, it is not clear whether dyslipidemia causes PC. The Mendelian randomization (MR) study aimed to investigate the causal role of lipid t...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87490-x |
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| author | Bohan Su Zhiyao Fan Jiexi Wu Hanxiang Zhan |
| author_facet | Bohan Su Zhiyao Fan Jiexi Wu Hanxiang Zhan |
| author_sort | Bohan Su |
| collection | DOAJ |
| description | Abstract Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and that lipid-lowering drugs may reduce the risk of PC. However, it is not clear whether dyslipidemia causes PC. The Mendelian randomization (MR) study aimed to investigate the causal role of lipid traits in pancreatic cancer and to assess the potential impact of lipid-lowering drug targets on pancreatic cancer. Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for PC were obtained from an independent GWAS datasets. Colocalization analyses were performed to validate the robustness of the results. No significant effect of lipid-lowering drug targets on PC risk was found. Genetic mimicry of lipoprotein lipase (LPL) was potentially associated with PC risks. Significant MR associations were observed in the discovery dataset (OR 1.64 [95% CI 1.24–2.16], p = 4.48*10–4) with PC in one dataset. However, the finding was not verified in the replication dataset. Our findings do not support dyslipidemia as a causal factor for PC. Among lipid-lowering drug targets, LPL is the potential drug target in PC. |
| format | Article |
| id | doaj-art-dde2b6c70eb44a7996c896b7c0101655 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-dde2b6c70eb44a7996c896b7c01016552025-01-26T12:33:55ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-87490-xGenetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization studyBohan Su0Zhiyao Fan1Jiexi Wu2Hanxiang Zhan3Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong UniversityDivision of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong UniversityDivision of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong UniversityDivision of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong UniversityAbstract Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and that lipid-lowering drugs may reduce the risk of PC. However, it is not clear whether dyslipidemia causes PC. The Mendelian randomization (MR) study aimed to investigate the causal role of lipid traits in pancreatic cancer and to assess the potential impact of lipid-lowering drug targets on pancreatic cancer. Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for PC were obtained from an independent GWAS datasets. Colocalization analyses were performed to validate the robustness of the results. No significant effect of lipid-lowering drug targets on PC risk was found. Genetic mimicry of lipoprotein lipase (LPL) was potentially associated with PC risks. Significant MR associations were observed in the discovery dataset (OR 1.64 [95% CI 1.24–2.16], p = 4.48*10–4) with PC in one dataset. However, the finding was not verified in the replication dataset. Our findings do not support dyslipidemia as a causal factor for PC. Among lipid-lowering drug targets, LPL is the potential drug target in PC.https://doi.org/10.1038/s41598-025-87490-xMendelian randomizationTGPancreatic cancereQTL |
| spellingShingle | Bohan Su Zhiyao Fan Jiexi Wu Hanxiang Zhan Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study Scientific Reports Mendelian randomization TG Pancreatic cancer eQTL |
| title | Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study |
| title_full | Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study |
| title_fullStr | Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study |
| title_full_unstemmed | Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study |
| title_short | Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study |
| title_sort | genetic association of lipid lowering drug target genes with pancreatic cancer a mendelian randomization study |
| topic | Mendelian randomization TG Pancreatic cancer eQTL |
| url | https://doi.org/10.1038/s41598-025-87490-x |
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