Genome-wide analyses identify 60 loci associated with liver triglyceride content.
研究对来自英国生物银行的71,488名欧洲血统参与者的磁共振成像衍生肝脏甘油三酯含量进行了大规模全基因组关联研究荟萃分析，样本量约为既往研究的2倍。共识别60个独立位点，其中31个为新发现；肝脏甘油三酯含量的单核苷酸多态性遗传率估计为25%。整合精细定位与基因优先排序分析为48个位点提名了候选效应基因。31个新发现变异中有14个在临床诊断的代谢功能障碍相关脂肪性肝病荟萃分析（42,163例病例和1,646,254例对照）中得到验证。肝脏甘油三酯含量多基因风险评分最高十分位者较最低十分位者肝硬化风险高2.71倍，肝细胞癌风险高7.47倍。与多基因风险评分相关的血浆蛋白富集于代谢重塑和炎症通路，遗传风险越高，肝脏富集蛋白特征越强，内脏脂肪特征越弱。研究细化了肝脏甘油三酯含量的遗传结构，将多基因易感性同下游代谢与炎症通路联系起来，为脂肪性肝病的遗传基础提供了见解。
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完整作者
Oveis Jamialahmadi、Shahir Mowlaei、Kyla Z Gelev、Rosellina M Mancina、Valentina Flagiello、Julia Kozlitina、Päivi Pajukanta、Luca Valenti、Stefano Romeo
作者机构
- Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. oveis.jamialahmadi@ki.se.
- Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden.
- Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy.
- Operative Research Unit of Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
- The Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA.
- Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
- Precision Medicine and Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
- Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. stefano.romeo@ki.se.
- Department of Endocrinology, Karolinska University Hospital, Huddinge, Sweden. stefano.romeo@ki.se.
- Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy. stefano.romeo@ki.se.
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. stefano.romeo@ki.se.
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. stefano.romeo@ki.se.
技术路线
MRI衍生肝脏甘油三酯含量数据（71,488名欧洲 ancestry UK Biobank参与者）→全基因组关联研究荟萃分析→识别60个独立位点（31个新位点）并估计SNP遗传力为25%→整合精细定位与基因优先级分析提名48个位点的候选效应基因→在临床诊断的代谢功能障碍相关脂肪性肝病荟萃分析（42,163例病例和1,646,254例对照）中验证31个新位点中的14个→多基因风险评分与肝硬化（OR 2.71）和肝细胞癌（OR 7.47）风险关联分析→与多基因风险评分相关的血浆蛋白通路富集分析（代谢重塑和炎症通路，肝脏富集蛋白特征增加、内脏脂肪特征减少）
最近 5 个完整年度引用趋势
不含 2026 年，仅展示最近 5 个完整年度。
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