当前位置: X-MOL 学术Nat. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease
Nature Medicine ( IF 58.7 ) Pub Date : 2024-12-09 , DOI: 10.1038/s41591-024-03284-0
Oveis Jamialahmadi, Antonio De Vincentis, Federica Tavaglione, Francesco Malvestiti, Ruifang Li-Gao, Rosellina M. Mancina, Marcus Alvarez, Kyla Gelev, Samantha Maurotti, Umberto Vespasiani-Gentilucci, Frits Richard Rosendaal, Julia Kozlitina, Päivi Pajukanta, François Pattou, Luca Valenti, Stefano Romeo

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903). Next, we generated two partitioned polygenic risk scores based on the presence of lipoprotein retention in the liver. The two polygenic risk scores suggest the presence of at least two distinct types of MASLD, one confined to the liver resulting in a more aggressive liver disease and one that is systemic and results in a higher risk of cardiometabolic disease. These findings shed light on the heterogeneity of MASLD and have the potential to improve the prediction of clinical trajectories and inform precision medicine approaches.



中文翻译:


分区多基因风险评分可识别代谢功能障碍相关脂肪性肝病的不同类型



代谢功能障碍相关脂肪性肝病 (MASLD) 的特征是肝脏和代谢综合征成分中脂质(主要是甘油三酯)过多,这可能导致肝硬化和肝癌。虽然有确凿的流行病学证据表明 MASLD 与心脏代谢疾病聚集,但 MASLD 的几个主要遗传危险因素不会增加心血管疾病的风险,这表明 MASLD 与心脏代谢紊乱之间没有因果关系。在这项工作中,我们利用内脏肥胖的测量确定了 27 个以前未知的与 MASLD 相关的遗传位点 (n = 36,394),其中 6 个在四个独立队列中重复 (n = 3,903)。接下来,我们根据肝脏中脂蛋白滞留的存在生成了两个分区的多基因风险评分。两个多基因风险评分表明至少存在两种不同类型的 MASLD,一种局限于肝脏,导致更具侵袭性的肝病,另一种是全身性的,导致心脏代谢疾病的风险更高。这些发现揭示了 MASLD 的异质性,并有可能改善对临床轨迹的预测并为精准医学方法提供信息。

更新日期:2024-12-09
down
wechat
bug