Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Oncology, Chongqing University Three Gorges Hospital, Chongqing, 404000, China.
Sci Rep. 2024 Oct 27;14(1):25644. doi: 10.1038/s41598-024-77105-2.
Non-alcoholic fatty liver disease (NAFLD) is a major global health concern, with its prevalence increasing steadily. While plasma proteins have been implicated in NAFLD, establishing causal relationships has been challenging due to confounding factors in observational studies. This study aims to explore the causal relationships between plasma proteins and NAFLD using Mendelian randomization (MR) analysis. We utilized genome-wide association study (GWAS) data from multiple sources to conduct MR analyses. Plasma protein data were obtained from the deCODE open database, and NAFLD data were sourced from the Finnish genetic sample collection (FinnGen). We performed MR analysis to identify plasma proteins causally related to NAFLD and explored the potential mediation effect of antibody-immune responses. Our MR analysis identified three plasma proteins-KNG1, MICB, and PKD2-with significant causal relationships to NAFLD. Mediation analysis further revealed that KNG1 negatively mediated the risk of NAFLD through Epstein-Barr virus EA-D antibody levels, while MICB and PKD2 positively mediated NAFLD risk through the same antibody levels. This study provides novel genetic evidence of causal relationships between specific plasma proteins and NAFLD risk. Measuring the levels of KNG1, MICB, PKD2, and Epstein-Barr virus EA-D antibody levels in patients may help clinicians assess NAFLD risk more accurately. Further clinical research is warranted to validate these findings and explore their potential therapeutic implications.
非酒精性脂肪性肝病（NAFLD）是一个主要的全球健康关注点，其患病率稳步上升。虽然血浆蛋白已被认为与 NAFLD 有关，但由于观察性研究中的混杂因素，确定因果关系一直具有挑战性。本研究旨在使用孟德尔随机化（MR）分析探讨血浆蛋白与 NAFLD 之间的因果关系。我们利用来自多个来源的全基因组关联研究（GWAS）数据进行 MR 分析。血浆蛋白数据来自 deCODE 开放数据库，NAFLD 数据来自芬兰遗传样本收集（FinnGen）。我们进行了 MR 分析，以确定与 NAFLD 有因果关系的血浆蛋白，并探讨了抗体免疫反应的潜在中介作用。我们的 MR 分析确定了三种与 NAFLD 有显著因果关系的血浆蛋白-KNG1、MICB 和 PKD2。中介分析进一步表明，KNG1 通过 Epstein-Barr 病毒 EA-D 抗体水平负向介导 NAFLD 的风险，而 MICB 和 PKD2 通过相同的抗体水平正向介导 NAFLD 风险。本研究提供了特定血浆蛋白与 NAFLD 风险之间因果关系的新遗传证据。测量患者的 KNG1、MICB、PKD2 和 Epstein-Barr 病毒 EA-D 抗体水平可能有助于临床医生更准确地评估 NAFLD 的风险。需要进一步的临床研究来验证这些发现并探讨其潜在的治疗意义。
