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.
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.
|Coté, Gregory A; Yadav, Dhiraj; Abberbock, Judah A et al. (2018) Recurrent Acute Pancreatitis Significantly Reduces Quality of Life Even in the Absence of Overt Chronic Pancreatitis. Am J Gastroenterol 113:906-912|
|Bellin, Melena D; Whitcomb, David C; Abberbock, Judah et al. (2017) Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States. Am J Gastroenterol 112:1457-1465|
|Machicado, Jorge D; Amann, Stephen T; Anderson, Michelle A et al. (2017) Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities. Am J Gastroenterol 112:633-642|
|Zator, Zachary; Whitcomb, David C (2017) Insights into the genetic risk factors for the development of pancreatic disease. Therap Adv Gastroenterol 10:323-336|
|Conwell, Darwin L; Banks, Peter A; Sandhu, Bimaljit S et al. (2017) Validation of Demographics, Etiology, and Risk Factors for Chronic Pancreatitis in the USA: A Report of the North American Pancreas Study (NAPS) Group. Dig Dis Sci 62:2133-2140|
|Whitcomb, David C (2016) Peering Into the ""Black Box"" of the Complex Chronic Pancreatitis Syndrome. Pancreas 45:1361-1364|
|Romagnuolo, Joseph; Talluri, Jyothsna; Kennard, Elizabeth et al. (2016) Clinical Profile, Etiology, and Treatment of Chronic Pancreatitis in North American Women: Analysis of a Large Multicenter Cohort. Pancreas 45:934-40|
|Wilcox, C Mel; Sandhu, Bimaljit S; Singh, Vikesh et al. (2016) Racial Differences in the Clinical Profile, Causes, and Outcome of Chronic Pancreatitis. Am J Gastroenterol 111:1488-1496|
|Wilcox, C Mel; Yadav, Dhiraj; Ye, Tian et al. (2015) Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings. Clin Gastroenterol Hepatol 13:552-60; quiz e28-9|
|Smith, Jill P; Whitcomb, David C; Matters, Gail L et al. (2015) Distribution of cholecystokinin-B receptor genotype between patients with pancreatic cancer and controls and its impact on survival. Pancreas 44:236-42|
Showing the most recent 10 out of 61 publications