NAPS2 Continuation - Genome-Wide Association Study of Pancreatitis

描述(申请人提供)：NAPS2-CONTINUE：胰腺炎全基因组关联研究北美胰腺炎研究2(NAPS2)是一项针对复发性急性和慢性胰腺炎的20个位点的前瞻性分子遗传学研究。超额完成1000门学科招生目标，还确定了近700门对照学科。这项研究的主要目的是调查6-10个候选基因的作用，以及主要环境因素(例如吸烟和饮酒)的影响。现在，技术的快速进步使全基因组关联研究(GWAS)能够以合理的成本进行。这次更新的目标是对患有胰腺炎症性疾病的受试者进行GWA。这项研究的力量将通过获得500名原始受试者的5年随访数据，以及招募另外500名慢性胰腺炎患者作为确诊人群来进一步推进。具体目标将是：目标1。对1000名复发性急性胰腺炎和慢性胰腺炎患者以及来自NAPS2研究的600名对照进行全基因组关联研究。目的2.再招募500名慢性胰腺炎患者进行验证性研究。目的3.对500例RAP和CP患者进行5年随访，以确定与疾病进展相关的因素。我们相信，这种全面、公正的方法将发现多个重要的基因和治疗靶点，以预防复发的急性胰腺炎、慢性胰腺炎和常见并发症。这一方法也将在将途径和关键机制与其他具有强大遗传基础的慢性炎症性疾病进行比较时发挥重要作用。因此，我们期待这一项目将为我们对胰腺疾病的理解提供重大进展。 公共卫生相关性：NAPS2全球气候变化：概述和意义。复发性急性胰腺炎和慢性胰腺炎都是胰腺炎症性疾病，目前尚无有效的治疗方法。在过去，大多数病例被归因于酒精中毒，这降低了对患者治疗和研究工作的热情。我们发现突变的胰蛋白酶原是一种易感基因，这让许多人重新评估了胰腺炎症的原因。我们组织了一项20个地点的研究(NAPS2)，纳入了1000多名复发性急性和慢性胰腺炎患者，以及近700名对照组，发现只有少数患者存在过量饮酒。这意味着其他罪魁祸首(包括基因变化)是重要的，但仍然是虚幻的。这项研究的目的是利用NAPS2研究中的DNA样本进行全基因组关联研究，以发现主要的遗传原因。了解胰腺炎的遗传基础将导致新的治疗方法，并有助于消除慢性胰腺炎只是酒鬼的疾病的耻辱。

DESCRIPTION (provided by applicant): NAPS2-Continuation: Genome-wide association study for pancreatitis The North American Pancreatitis Study 2 (NAPS2) was a 20-site, prospective molecular genetics study of recurrent acute and chronic pancreatitis. The enrollment target of 1000 subjects was exceeded, and nearly 700 control subjects were also ascertained. The primary purpose of the study was to investigate the role of 6-10 candidate genes, plus the influence of major environmental factors (e.g. tobacco smoking and alcohol consumption). Now, the rapid advances in technology allow for genome-wide association studies (GWAS) to be conducted at a reasonable cost. The goal of this renewal is to conduct a GWAS of subjects with inflammatory diseases of the pancreas. The power of the study will be further advanced by obtaining 5 year follow-up data on 500 of the original subjects, plus the recruitment of an additional 500 patients with chronic pancreatitis as a confirmatory population. The specific aims will be: Aim 1. To conduct a genome-wide association studies on 1000 subjects with recurrent acute pancreatitis and chronic pancreatitis plus 600 controls from the NAPS2 study. Aim 2. To recruit an additional 500 subjects with chronic pancreatitis for confirmatory studies. Aim 3. To re-ascertain 500 subjects with RAP and CP from the original centers with > 5 years of follow-up to determine factors associated with rates of diseases progression. We believe that this comprehensive, unbiased approach will uncover multiple important genes and therapeutic targets to prevent recurrent acute pancreatitis, chronic pancreatitis and common complications. This approach will also be important in comparing pathways and key mechanism with other chronic inflammatory disorders with strong genetic basis. Thus, we expect this project to provide major advances in our understanding of pancreatic diseases. PUBLIC HEALTH RELEVANCE: NAPS2 GWAS: Overview and significance. Both recurrent acute and chronic pancreatitis are inflammatory diseases of the pancreas for which there is no effective treatment. In the past, the majority of cases were attributed to alcoholism, which lowered enthusiasm for patient treatment and for research efforts. Our discovery of mutant trypsinogen as a susceptibility gene caused many to reassess the causes of pancreatic inflammation. We organized a 20 site study (NAPS2) to enroll over 1000 cases of recurrent acute and chronic pancreatitis, plus nearly 700 controls and discovered that excessive alcohol drinking is only found in a minority of patients. This means that other culprits (including genetic changes) are important, but remain illusive. The purpose of this study is to use DNA samples from the NAPS2 study to conduct a genome-wide association study (GWAS) to discover the major genetic causes. Knowledge of the genetic basis of pancreatitis will lead to new treatments, and help remove the stigma that chronic pancreatitis is only a disease of drunkards.