解码遗传学/安进公司Kari Stefansson和Gardar Sveinbjornsson共同合作近期取得重要工作进展，他们进行了非酒精性脂肪肝的多组学研究。相关论文2022年10月24日在线发表于《自然—遗传学》杂志上。
研究人员进行了NAFL、肝硬化和肝细胞癌的全基因组关联研究，并将研究结果与基因表达和蛋白质组学数据结合起来。对于NAFL，研究人员利用了9491个临床病例和从36116张肝脏磁共振图像中提取的质子密度脂肪分数。研究人员确定了18个与NAFL相关的序列变异和4个与肝硬化相关的序列变异，并在MTARC1和GPAM中发现了罕见的、保护性的、可预测的功能丧失变异，强调它们是潜在的药物靶点。
他们利用mRNA表达、剪接和预测编码效应来识别16个假定的致病基因，其中许多基因与脂质代谢有关。研究人员分析了35,559名冰岛人的4,907种血浆蛋白的水平和47,151名英国生物库参与者的1,459种蛋白，确定了参与疾病发病机制的多种蛋白。蛋白质组学还可以区分NAFL和肝硬化。本研究为非酒精性脂肪肝无创评估的发展和新治疗方案的开发提供了见解。
据介绍，非酒精性脂肪肝（NAFL）及其并发症是日益严重的健康问题。
附：英文原文
Title: Multiomics study of nonalcoholic fatty liver disease
Author: Sveinbjornsson, Gardar, Ulfarsson, Magnus O., Thorolfsdottir, Rosa B., Jonsson, Benedikt A., Einarsson, Eythor, Gunnlaugsson, Gylfi, Rognvaldsson, Solvi, Arnar, David O., Baldvinsson, Magnus, Bjarnason, Ragnar G., Eiriksdottir, Thjodbjorg, Erikstrup, Christian, Ferkingstad, Egil, Halldorsson, Gisli H., Helgason, Hannes, Helgadottir, Anna, Hindhede, Lotte, Hjorleifsson, Grimur, Jones, David, Knowlton, Kirk U., Lund, Sigrun H., Melsted, Pall, Norland, Kristjan, Olafsson, Isleifur, Olafsson, Sigurdur, Oskarsson, Gudjon R., Ostrowski, Sisse Rye, Pedersen, Ole Birger, Snaebjarnarson, Auunn S., Sigurdsson, Emil, Steinthorsdottir, Valgerdur, Schwinn, Michael, Thorgeirsson, Gudmundur, Thorleifsson, Gudmar, Jonsdottir, Ingileif, Bundgaard, Henning, Nadauld, Lincoln, Bjornsson, Einar S., Rulifson, Ingrid C., Rafnar, Thorunn, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Sulem, Patrick, Gudbjartsson, Daniel F., Holm, Hilma, Stefansson, Kari
Issue&Volume: 2022-10-24
Abstract: Nonalcoholic fatty liver (NAFL) and its sequelae are growing health problems. We performed a genome-wide association study of NAFL, cirrhosis and hepatocellular carcinoma, and integrated the findings with expression and proteomic data. For NAFL, we utilized 9,491 clinical cases and proton density fat fraction extracted from 36,116 liver magnetic resonance images. We identified 18 sequence variants associated with NAFL and 4 with cirrhosis, and found rare, protective, predicted loss-of-function variants in MTARC1 and GPAM, underscoring them as potential drug targets. We leveraged messenger RNA expression, splicing and predicted coding effects to identify 16 putative causal genes, of which many are implicated in lipid metabolism. We analyzed levels of 4,907 plasma proteins in 35,559 Icelanders and 1,459 proteins in 47,151 UK Biobank participants, identifying multiple proteins involved in disease pathogenesis. We show that proteomics can discriminate between NAFL and cirrhosis. The present study provides insights into the development of noninvasive evaluation of NAFL and new therapeutic options.
DOI: 10.1038/s41588-022-01199-5
Source: https://www.nature.com/articles/s41588-022-01199-5
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
