Abstract：
OBJECTIVE: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs).
METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836).
RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models.
CONCLUSIONS: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.
METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836).
RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models.
CONCLUSIONS: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.
摘要：
目的：原发性胆汁性胆管炎（PBC）是一种常伴有多系统损害的自身免疫性疾病。本研究旨在探讨基因预测的PBC与糖尿病之间的因果关系。以及多种心血管疾病（CVDs）。
方法：使用来自欧洲肝脏研究协会的24,510名欧洲血统个体的PBC的全基因组关联研究（GWAS）汇总数据来鉴定遗传预测的PBC。我们进行了2样本单变量孟德尔随机化（SVMR）和多变量孟德尔随机化（MVMR），以评估PBC对糖尿病的影响（N=17,685至318,014）和遗传联盟的20个CVD（N=171,875至1,030,836）。
结果：SVMR提供了基因预测的PBC与1型糖尿病（T1D）风险增加相关的证据，2型糖尿病（T2D），心肌梗死（MI），心力衰竭(HF),高血压,心房颤动(AF),中风,缺血性卒中,和小血管缺血性中风。此外,没有证据表明PBC与冠状动脉粥样硬化之间存在因果关系.在MVMR分析中，PBC对T1D保持独立作用，HF,MI,和小血管缺血性中风在大多数模型。
结论：我们的发现揭示了PBC对糖尿病和7种心血管疾病的因果效应，未检测到PBC与冠状动脉粥样硬化之间的因果关系。
方法：使用来自欧洲肝脏研究协会的24,510名欧洲血统个体的PBC的全基因组关联研究（GWAS）汇总数据来鉴定遗传预测的PBC。我们进行了2样本单变量孟德尔随机化（SVMR）和多变量孟德尔随机化（MVMR），以评估PBC对糖尿病的影响（N=17,685至318,014）和遗传联盟的20个CVD（N=171,875至1,030,836）。
结果：SVMR提供了基因预测的PBC与1型糖尿病（T1D）风险增加相关的证据，2型糖尿病（T2D），心肌梗死（MI），心力衰竭(HF),高血压,心房颤动(AF),中风,缺血性卒中,和小血管缺血性中风。此外,没有证据表明PBC与冠状动脉粥样硬化之间存在因果关系.在MVMR分析中，PBC对T1D保持独立作用，HF,MI,和小血管缺血性中风在大多数模型。
结论：我们的发现揭示了PBC对糖尿病和7种心血管疾病的因果效应，未检测到PBC与冠状动脉粥样硬化之间的因果关系。
