Wu Huan, Wu Long, Zhang Quan, Li Can, Li Hai-Yang, Zhang Bao-Fang
Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Department of Anus and Intestinal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Front Nutr. 2024 Jul 31;11:1292954. doi: 10.3389/fnut.2024.1292954. eCollection 2024.
Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD.
We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels ( = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed.
In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [ = 0.624 (0.336-1.160), = 0.136] and ALD had no causal effect on circulating VD [ = 0.997 (0.986-1.008), = 0.555]. No heterogeneity or pleiotropy was observed ( > 0.05). Other MR methods also agreed with IVW results.
This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.
众多观察性研究表明维生素D（VD）与酒精性肝病（ALD）之间存在关联。然而，来自随机对照试验（RCT）的充分证据证实这种相关性的却很少，因此这种关系的因果性仍不明确。为克服传统观察性研究的缺点，我们进行了双样本双向孟德尔随机化（MR）分析以确定VD与ALD之间的因果关系。
我们利用了来自全基因组关联研究（GWAS）的关于VD和ALD的汇总统计数据集。我们选择了测量循环VD水平的遗传工具（n = 64,979），并从GWAS中检索了ALD统计数据，其中包括1416例病例和217376名健康对照，同时排除了诸如非酒精性脂肪性肝病、中毒性肝病和病毒性肝炎等慢性肝病。随后，使用逆方差加权（IVW）随机效应模型进行MR分析以获得效应估计值。使用 Cochr an's Q统计量和MR-Egger回归截距分析来评估多效性。还使用MR Egger、加权中位数、简单模式和加权模式方法进行了敏感性分析。采用留一法分析来识别具有潜在效应的单核苷酸多态性（SNP）。还进行了反向MR分析。
在IVW中，我们的MR分析纳入了21个独立的SNP，循环VD水平对ALD没有因果效应[比值比（OR）= 0.624（0.336 - 1.160），P = 0.136]，并且ALD对循环VD也没有因果效应[OR = 0.997（0.986 - 1.008），P = 0.555]。未观察到异质性或多效性（P > 0.05）。其他MR方法也与IVW结果一致。
本研究提供了基因预测的循环维生素D水平与ALD之间的因果关系，并为ALD的遗传学提供了新的见解。
