Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

Abstract

Background:

Nonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear.

Methods:

We adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide association studies (GWASs).

Results:

We retrieved GSD SNPs attributed to 10,520 cases and 361,194 controls and validated our estimates using GWAS summary data from UK Biobank. We also performed sex-stratified analyses. Based on the summary estimates of 41, 59, 35, and 2 SNPs for low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), triglycerides (TGs), and NAFLD, respectively, we found no evidence of a causal relationship between genetically-predicted lipid profiles and GSD. The odds ratios were 0.995 for LDLC [95% confidence interval (CI): 0.994-0.998] per 0.98 mmol/L, 0.999 for HDLC (95% CI: 0.996-1.003) per 0.41 mmol/L, 0.997 for TGs (95% CI: 0.994-1.001) per 1 mmol/L, and 0.993 for NAFLD (95% CI: 0.984-1.003). No evidence of associations between lipid profile s and GSD in validation MR analyses or the sex-stratification analyses was noted.

Conclusions:

Genetically predicted hyperlipidemia or NAFLD is not causally associated with GSD.

• Authors: Xiaofeng Yuan, Haitian Chen, Kaining Zeng, Jiaqi Xiao, Jiaqing Liu, Guowang Lin, Jiebin Zhang, Tongyu Lu, Jianye Cai, Jia Yao, Yingcai Zhang, Xin Sui, Jinliang Liang, Jun Zheng
• Journal: Annals of translational medicine (Ann Transl Med) Vol. 10 Issue 15 Pg. 818 (Aug 2022) ISSN: 2305-5839 [Print] China
• PMID: 36035003 (Publication Type: Journal Article)
• Copyright: 2022 Annals of Translational Medicine. All rights reserved.