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在开始的结尾。
DOI：
10.1055/s-0031-1276640
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发表时间：
2011
影响因子：
4.2
通讯作者：
Lazaridis,KonstantinosN
中科院分区：
文献类型：
--
作者：
Karlsen,TomH;Lazaridis,KonstantinosN
在过去的十年中，HapMap 项目 (http://hapmap.ncbi.nlm.nih.gov/) 加速了复杂疾病遗传学领域的进展，该项目导致了密集基因分型阵列的发展，以及由专门研究人员创建的患者大型 DNA 存储库的可用性。这些资源导致通过全基因组关联研究（GWAS）发现了人类疾病的新易感位点。这些“先验研究”（从传统的假设特定研究方法的转变）使得能够采用公正的方法来破译肝脏疾病的遗传结构。在本期肝病研讨会上，一组专家：(1) 总结了近期不同肝病的遗传学研究结果，包括 GWAS 的结果；(2) 检验这些观察结果的科学和临床影响； (3) 提出了未来的方法学途径，以更好地描述遗传在肝脏疾病中的作用。我们感谢贡献者对指定主题的精彩评论。 Mark Thursz 及其同事撰写了一篇关于“了解慢性乙型和丙型肝炎的宿主遗传学”的概要。病毒性肝炎的传统疗法主要集中在传染原上。最近发现 IL-28B 基因型是宿主治疗反应和丙型肝炎病毒感染自发消退的主要决定因素，这是基因发现如何彻底改变临床实践的最好例子。 Christopher Day 及其同事撰写了一篇关于“酒精性和非酒精性脂肪性肝病的遗传学”的综述。讨论了这两种实体的易感性和修饰基因，包括参与从脂肪性肝炎到纤维化和肝细胞癌的疾病进展的遗传位点。 Gideon Hirschfield 和 Pietro Invernizzi 概述了“原发性胆汁性肝硬化的遗传学进展”。最近的两项 GWAS 以及著名的候选基因研究，对原发性胆汁性肝硬化的发病机制进行了回顾和相关研究，并对未来的研究提出了建议，以更好地描述这种疾病。 Frank Lammert 及其同事介绍了“剖析胆囊结石形成的遗传异质性”的最新进展。提高对胆结石疾病患者亚组的了解可能会产生重大的临床影响。讨论了胆结石的易感基因以及这些观察结果对患者咨询的影响。 Jean-Charles Nault 和 Jessica Zucman-Rossi 对“肝胆癌发生的遗传学”进行了概述。恶性肿瘤是晚期肝病的可怕并发症。讨论了肝细胞癌和胆管癌致癌的分子途径以及靶向治疗的前景。 Tom Hemming Karlsen 和 Arthur Kaser 撰写了一篇关于“破译原发性硬化性胆管炎的遗传易感性”的综述。迄今为止，原发性硬化性胆管炎的病理学仍然难以捉摸。以有组织的方式呈现当前疾病位点的功能注释以及将这些发现转化为临床实践的挑战。 Aftab Ala 和 Michael Schilsky 撰写了一篇关于“遗传性肝病中肝损伤的基因修饰因素”的评论。这个具有挑战性的主题涵盖了威尔逊病、遗传性血色素沉着病和 a-1 抗胰蛋白酶缺乏症，并强调了临床观察到的遗传对疾病变异性的影响。最后，Brian Juran 和 Konstantinos Lazaridis 提供了“后 GWAS 时代的基因组学”的概念框架。作者描述了从……中吸取的教训。
In the past decade, progress in the field of complex disease genetics has been accelerated by the HapMap project (http://hapmap. ncbi. nlm. nih. gov/), which led to the development of dense genotyping arrays, and by the availability of large DNA repositories of patients created by dedicated investigators. Such resources have led to the discovery of novel susceptibility loci of human disease by means of genome-wide association studies (GWAS). These ‘‘a priori studies’’(a shift from the traditional approach of hypothesis-specific research) have allowed an unbiased method to decipher the genetic architecture of liver disorders. In this issue of Seminars in Liver Disease, a group of experts:(1) summarizes the findings of recent genetic studies, including GWAS, in different liver diseases;(2) examines the scientific and clinical ramifications of these observations; and (3) proposes future methodological approaches to better delineate the genetic contribution in liver diseases. We are indebted to our contributors for superb reviews on the assigned topics. Mark Thursz and colleagues have written a synopsis on ‘‘Understanding the Host Genetics of Chronic Hepatitis B and C.’’Traditional therapies for viral hepatitides have focused on the infectious agent. The recent identification of the IL-28B genotype as a major determinant of host treatment response and spontaneous resolution of infection of patients with hepatitis C virus is the best example of how genetic discoveries can revolutionize clinical practice. Christopher Day and colleagues have contributed a review on ‘‘Genetics of Alcoholic and Nonalcoholic Fatty Liver Disease.’’Susceptibility and modifier genes of both entities are discussed, including genetic loci that participate in disease progression from steatohepatitis to fibrosis and to hepatocellular cancer. Gideon Hirschfield and Pietro Invernizzi provide an overview on ‘‘Progress in the Genetics of Primary Biliary Cirrhosis.’’Two recent GWAS, as well as notable candidate gene studies, are reviewed and related to the pathogenesis of primary biliary cirrhosis with suggestions on future studies to better delineate this disorder. Frank Lammert and colleagues present an update on ‘‘Dissecting the Genetic Heterogeneity of Gallbladder Stone Formation.’’Improving the understanding of subgroups of patients with gallstone disease could have significant clinical impact. Susceptibility genes for gallstones are discussed along with ramifications of these observations on patient counseling. Jean-Charles Nault and Jessica Zucman-Rossi give an overview on ‘‘Genetics of Hepatobiliary Carcinogenesis.’’Malignancy is a dreaded complication of advanced liver disease. Molecular pathways of carcinogenesis in both hepatocellular carcinoma and cholangiocarcinoma are discussed along with the promise of targeted therapies. Tom Hemming Karlsen and Arthur Kaser contribute a review on ‘‘Deciphering the Genetic Predisposition to Primary Sclerosing Cholangitis.’’To date, the pathobiology of primary sclerosing cholangitis remains elusive. Functional annotations of the current disease loci are presented in an organized fashion as well as the challenges of translating these findings into clinical practice. Aftab Ala and Michael Schilsky have written a review on ‘‘Genetic Modifiers of Liver Injury in Hereditary Liver Disease.’’This challenging topic covers Wilson disease, hereditary hemochromatosis, and a-1 anti-trypsin deficiency, and underscores the influence of genetics on disease variability as observed in the clinic. Finally, Brian Juran and Konstantinos Lazaridis provide a conceptual framework on ‘‘Genomics in the Post-GWAS Era.’’The authors describe the lessons learned from the …