血脂谱变化与胆结石病风险之间的因果关联：一项两样本孟德尔随机化研究。
Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.
作者信息
Yuan Xiaofeng, Chen Haitian, Zeng Kaining, Xiao Jiaqi, Liu Jiaqing, Lin Guowang, Zhang Jiebin, Lu Tongyu, Cai Jianye, Yao Jia, Zhang Yingcai, Sui Xin, Liang Jinliang, Zheng Jun
机构信息
Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of General Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
出版信息
Ann Transl Med. 2022 Aug;10(15):818. doi: 10.21037/atm-21-4007.
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.
背景
在观察性研究中，非酒精性脂肪性肝病（NAFLD）与胆结石病（GSD）有关；然而，某些血脂谱与GSD之间的关系仍不清楚。
方法
我们采用两样本孟德尔随机化（MR）框架，应用不同的统计方法来评估血脂谱与GSD之间的因果关系。我们从先前单独的全基因组关联研究（GWAS）中确定了血脂和NAFLD的单核苷酸多态性（SNP）。
结果
我们检索了归因于10520例病例和361194例对照的GSD SNP，并使用英国生物银行的GWAS汇总数据验证了我们的估计值。我们还进行了性别分层分析。分别基于低密度脂蛋白胆固醇（LDLC）、高密度脂蛋白胆固醇（HDLC）、甘油三酯（TGs）和NAFLD的41、59、35和2个SNP的汇总估计值，我们没有发现遗传预测的血脂谱与GSD之间存在因果关系的证据。每0.98 mmol/L的LDLC的优势比为0.995 [95%置信区间（CI）：0.994 - 0.998]，每0.41 mmol/L的HDLC的优势比为0.999（95% CI：0.996 - 1.003），每1 mmol/L的TGs的优势比为0.997（95% CI：0.994 - 1.001），NAFLD的优势比为0.993（95% CI：0.984 - 1.003）。在验证性MR分析或性别分层分析中，未发现血脂谱与GSD之间存在关联的证据。
结论
遗传预测的高脂血症或NAFLD与GSD无因果关系。
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