NDLI: Mendelian randomization study of circulating lipids and biliary tract cancer among East Asians

Content Provider	Springer Nature : BioMed Central
Author	Wang, Jun Zhuge, Jinke Feng, Dongxu Zhang, Bo Xu, Jianying Zhao, Dongkang Fei, Zhewei Huang, Xia Shi, Wenjie
Abstract	Background Associations of High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (CHL), and triglyceride (TRG) concentrations with risk of biliary tract cancer (BtC) were conflicting in observational studies. We aim to investigate the causal link between circulating lipids and BtC using genetic information. Methods Single nucleotide polymorphisms of the four circulating lipids (n = 34,421) and BtC (418 cases and 159,201 controls) were retrieved from two independent GWAS studies performed in East Asian populations. Two-sample univariate and multivariate Mendelian Randomization (MR) analyses were conducted to determine the causal link between circulating lipids and BtC. Results No significant horizontal pleiotropy was detected for all circulating lipids according to the MR-PRESSO global test (P = 0.458, 0.368, 0.522, and 0.587 for HDL, LDL, CHL, and TRG, respectively). No significant evidence of heterogeneity and directional pleiotropy was detected by the Cochran’s Q test and MR-Egger regression. Univariate MR estimates from inverse variance weighting method suggested that one standard deviation (1-SD) increase of inverse-normal transformed HDL (OR = 1.38, 95% CI 0.98–1.94), LDL (OR = 1.46, 95% CI 0.96–2.23), and CHL (OR = 1.34, 95% CI 0.83–2.16) were not significantly associated with BtC risk. Whereas 1-SD increase of inverse-normal transformed TRG showed a significantly negative association with BtC risk (OR = 0.48, 95% CI 0.31–0.74). In multivariate MR analyses including all the four lipid traits, we found that 1-SD increase of LDL and TRG was significantly associated with elevated (OR = 1.32, 95% CI 1.04–2.01) and decreased (OR = 0.54, 95% CI 0.42–0.68) risk of BtC, respectively. Conclusion Circulating lipids, particularly LDL and TRG, may have roles in the development of BtC. However, the results of this study should be replicated in MR with larger GWAS sample sizes for BtC.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-09382-x.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-09382-x
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-03-15
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Biliary tract cancer Mendelian randomization Lipid HDL LDL Triglyceride Cholesterol Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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