Nonalcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (eg, PNPLA3, TM6SF2, and SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis, and cancer over time. Here, we summarize key NAFLD risk genes and illustrate their interactions in a 3-dimensional "risk space." Although NAFLD genomics sometimes appears to be "lost in translation," we envision clinical utility in trial design, outcome prediction, and NAFLD surveillance.

中文翻译：

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非酒精性脂肪肝疾病轨迹的遗传预测：PNPLA3及以后。

非酒精性脂肪肝疾病（NAFLD）即将成为肝病的主要原因。NAFLD在环境因素和遗传易感性之间的界面上发展。全基因组关联研究，然后是全基因组分析，导致了遗传风险变异（例如PNPLA3，TM6SF2和SERPINA1）的鉴定以及涉及脂肪肝疾病病理生物学的关键途径。功能研究增进了我们对这些遗传因素以及随着时间的推移从脂肪积累到纤维化，肝硬化和癌症的轨迹的分子机制的理解。在这里，我们总结了关键的NAFLD风险基因，并说明了它们在3维“风险空间”中的相互作用。尽管NAFLD基因组学有时似乎“失去了翻译”，但我们认为临床设计可用于试验设计，