Multisystem health comorbidity networks of metabolic dysfunction-associated steatotic liver disease.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-11-08 Epub Date: 2024-08-07 DOI:10.1016/j.medj.2024.07.013

Fangyuan Jiang, Lijuan Wang, Haochao Ying, Jing Sun, Jianhui Zhao, Ying Lu, Zilong Bian, Jie Chen, Aiping Fang, Xuehong Zhang, Susanna C Larsson, Christos S Mantzoros, Weilin Wang, Shuai Yuan, Yuan Ding, Xue Li

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引用次数: 0

Abstract

Background: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.

Methods: A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.

Findings: The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.

Conclusions: This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.

Funding: X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).

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代谢功能障碍相关脂肪性肝病的多系统健康合并症网络。

背景：代谢功能障碍相关性脂肪性肝病（MASLD）在全球造成的负担越来越重，但其随后对健康造成的影响尚未得到彻底研究：方法：在英国生物库的361,021名欧洲人中开展了一项全表型关联研究，以绘制MASLD与948种独特临床结果的关联图。应用疾病轨迹和并发症分析，可视化与 MASLD 发生相关的多种并发症的顺序模式。利用芬兰基因研究和国际联盟的数据，通过双样本孟德尔随机分析进一步复制了观察性和多基因表型全分析共同验证的关联：观察性和多基因表型关联研究揭示了MASLD与96种肝内和肝外疾病的关联，包括循环系统疾病、代谢性疾病、泌尿生殖系统疾病、神经系统疾病、胃肠道疾病和血液系统疾病。MASLD相关肝外合并症的序列模式主要出现在循环系统疾病、代谢性疾病和炎症性疾病中。孟德尔随机分析支持MASLD与几种肝内疾病、代谢性疾病、心脑血管疾病和腹水风险之间的因果关系，但未发现与神经系统疾病的关联：这项研究阐明了MASLD的多系统并发症和健康后果，有助于开发针对不同途径的综合干预措施，促进MASLD患者的健康：X.L.受浙江省杰出青年学者自然科学基金（LR22H260001）和国家自然科学基金（82204019）资助，Y.D.受浙江省中医药科技计划重点项目（GZY-ZJ-KJ-24077）和国家自然科学基金（82001673和82272860）资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.