PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 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.
UNASSIGNED: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results.
UNASSIGNED: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.
UNASSIGNED: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 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.
UNASSIGNED: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results.
UNASSIGNED: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.
摘要：
■许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,随机对照试验(RCTs)证实这种相关性的足够证据很少，从而使这种关系的因果关系变得模棱两可。为了克服传统观测研究的不足,我们进行了双样本双向孟德尔随机化(MR)分析,以确定VD和ALD之间的因果关系.
■我们利用来自全基因组关联研究（GWAS）的VD和ALD的汇总统计数据集。我们选择了测量循环VD水平的遗传仪器(n=64,979)，并从GWAS检索ALD统计数据，包括1,416例病例和217,376例健康对照，同时排除慢性肝病，如非酒精性脂肪性肝病，中毒性肝病,和病毒性肝炎。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。Cochran的Q统计量和MR-Egger回归截距分析用于评估多效性。使用MREgger进行敏感性分析，加权中位数，简单模式，和加权模式方法也进行了。使用留一分析来鉴定具有潜在作用的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没有因果关系[OR=0.624（0.336-1.160），p=0.136]，ALD对循环VD没有因果关系[OR=0.997（0.986-1.008），p=0.555]。没有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。
■这项研究提供了遗传预测的循环维生素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。
■我们利用来自全基因组关联研究（GWAS）的VD和ALD的汇总统计数据集。我们选择了测量循环VD水平的遗传仪器(n=64,979)，并从GWAS检索ALD统计数据，包括1,416例病例和217,376例健康对照，同时排除慢性肝病，如非酒精性脂肪性肝病，中毒性肝病,和病毒性肝炎。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。Cochran的Q统计量和MR-Egger回归截距分析用于评估多效性。使用MREgger进行敏感性分析，加权中位数，简单模式，和加权模式方法也进行了。使用留一分析来鉴定具有潜在作用的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没有因果关系[OR=0.624（0.336-1.160），p=0.136]，ALD对循环VD没有因果关系[OR=0.997（0.986-1.008），p=0.555]。没有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。
■这项研究提供了遗传预测的循环维生素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。
