Non-alcoholic fatty liver disease (NAFLD) is now recognised as the most common liver disease worldwide. It encompasses a broad spectrum of conditions, from simple steatosis, through non-alcoholic steatohepatitis, to fibrosis and ultimately cirrhosis and hepatocellular carcinoma. A hallmark of NAFLD is the substantial inter-patient variation in disease progression. NAFLD is considered a complex disease trait such that interactions between the environment and a susceptible polygenic host background determine disease phenotype and influence progression. Recent years have witnessed multiple genome-wide association and large candidate gene studies, which have enriched our understanding of the genetic basis of NAFLD. Notably, the I148M PNPLA3 variant has been identified as the major common genetic determinant of NAFLD. Variants with moderate effect size in TM6SF2, MBOAT7 and GCKR have also been shown to have a significant contribution. The premise for this review is to discuss the status of research into important genetic and epigenetic modifiers of NAFLD progression. The potential to translate the accumulating wealth of genetic data into the design of novel therapeutics and the clinical implementation of diagnostic/prognostic biomarkers will be explored. Finally, personalised medicine and the opportunities for future research and challenges in the immediate post genetics era will be illustrated and discussed.

中文翻译：

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NAFLD 和 NASH 的遗传学和表观遗传学：临床影响

非酒精性脂肪性肝病 (NAFLD) 现在被认为是全世界最常见的肝脏疾病。它涵盖了广泛的病症，从简单的脂肪变性到非酒精性脂肪性肝炎，再到纤维化和最终的肝硬化和肝细胞癌。NAFLD 的一个标志是疾病进展的大量患者间变异。NAFLD 被认为是一种复杂的疾病特征，因此环境与易感多基因宿主背景之间的相互作用决定了疾病表型并影响进展。近年来见证了多个全基因组关联和大型候选基因研究，丰富了我们对 NAFLD 遗传基础的理解。值得注意的是，I148M PNPLA3 变体已被确定为 NAFLD 的主要常见遗传决定因素。在 TM6SF2、MBOAT7 和 GCKR 中具有中等效应大小的变体也已被证明具有显着贡献。本综述的前提是讨论对 NAFLD 进展的重要遗传和表观遗传修饰因子的研究现状。将探索将积累的大量遗传数据转化为新疗法设计和诊断/预后生物标志物的临床实施的潜力。最后，将说明和讨论个性化医疗以及紧接后遗传学时代未来研究和挑战的机会。将探索将积累的大量遗传数据转化为新疗法设计和诊断/预后生物标志物的临床实施的潜力。最后，将说明和讨论个性化医疗以及紧接后遗传学时代未来研究和挑战的机会。将探索将积累的大量遗传数据转化为新疗法设计和诊断/预后生物标志物的临床实施的潜力。最后，将说明和讨论个性化医疗以及紧接后遗传学时代未来研究和挑战的机会。