Genetic Epidemiology of GERD in COPD

COPD 中 GERD 的遗传流行病学

• 批准号: 10605652
• 负责人: Ava C Wilson
• 金额: $ 1.87万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-02 至 2023-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10605652
• 关键词: Area; Bioinformatics; Biometry; Bronchial Spasm; Cause of Death; Chronic; Chronic Disease; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Cloud Computing; Cohort Studies; Complement; Coughing; Data; Databases; Development; Diagnosis; Disease; Doctor of Philosophy; Environment; Epidemiology; Etiology; Exhibits; Exposure to; Facilities and Administrative Costs; Fibroblasts; Foundations; Frequencies; Functional disorder; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; Gastric Acid; Gastroesophageal reflux disease; Gastrointestinal Diseases; Genes; Genetic; Genetic Predisposition to Disease; Genomic Segment; Genomics; Goals; Health; Health Expenditures; Heritability; Hospitalization; Individual; Inflammation; Intervention; Intra-abdominal; Knowledge; Longitudinal cohort; Longitudinal, observational study; Lung; Lung diseases; Mediating; Mediation; Mentors; Methodology; Methods; Modeling; Molecular; Molecular Biology; Molecular Genetics; Myofibroblast; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Prevalence; Production; Pulmonary Fibrosis; Pulmonary aspiration of gastric contents; Pulmonology; Quality Control; Quality of life; Reflex action; Reflux; Research; Research Personnel; Risk; Role; Scientist; Signal Pathway; Signal Transduction; Solid; Training; Training Programs; Trans-Omics for Precision Medicine; Transforming Growth Factor beta; United States National Institutes of Health; Variant; abdominal pressure; biobank; career; career development; catalyst; cohort; comorbidity; computational platform; disease classification; disorder subtype; drug repurposing; experience; former smoker; genetic epidemiology; genetic risk factor; genetic variant; genome sequencing; genome wide association study; genomic data; health science research; improved; insight; mortality; novel; persistent symptom; phenotypic data; pleiotropism; pressure; pulmonary function; pulmonary symptom; research and development; research study; responsible research conduct; skills; tool; whole genome

PROJECT SUMMARY The purpose of this NIH F31 application is to obtain support for the PI, Ava Wilson, for mentored research and career development activities within her PhD training that will strengthen her potential to become an independent research scientist in the pulmonary field. The project goal is to develop skills in genetic epidemiology, bioinformatics, statistical genetics, and pulmonology that will allow her to estimate the genetic co-heritability of Chronic Obstructive Pulmonary Disease (COPD) and Gastroesophageal Reflux Disease (GERD) (Aim 1). GERD is a prevalent comorbidity in COPD and both conditions are heritable (estimates of genetic heritability for COPD and GERD as high as 38% and 43%), however, the co-heritability of GERD and COPD has not been investigated. Genome-wide association studies (GWAS) have identified genetic variants associated with GERD and COPD individually, however, there exists a paucity of in-depth genomic analyses of comorbid GERD and COPD. To fill this gap, the PI will perform analyses to identify genomic variants and regions associated with prevalent GERD in COPD and conduct mediation analysis to determine the extent to which pleiotropy contributes to comorbid GERD and COPD (Aims 2A and 2B). The interaction between GERD and COPD has long been recognized as excess gastric acid as part of GERD can exacerbate COPD and symptoms of COPD such as cough can contribute to GERD. Heritability modeling, genomic analyses and causal mediation modeling of whole genome sequencing (WGS) and GWAS data from TOPMed, All of Us, and the UK Biobank cohorts with deep phenotype data will be performed using state-of-the-art cloud computing environments. The central hypothesis is overlapping genetic and/or molecular pathways contribute to a shared etiology in COPD and GERD, which has not been fully explored. The long-term objective of the PI’s research is to understand how the etiology of GERD and COPD overlap to provide opportunities for novel interventions and to facilitate drug repurposing. UAB is nationally recognized for its health science research and training programs, specifically in genomics and pulmonary disease. The proposed training plan for the PI is sponsored by her project mentors, Drs. Merry-Lynn McDonald and Hemant Tiwari. Included in the training plan are experiences to help the PI develop in the following major areas: 1) rigorous research in the pulmonary field, including developing expertise in COPD and GERD epidemiology, principles of scientific integrity and responsible conduct of research, and scientific expertise in pulmonary and gastrointestinal diseases; 2) genetic epidemiology, including advanced methodology, and interpretation of results; 3) advanced biostatistical analyses and statistical genetics; 4) career and professional development, and data presentation; and 5) exposure to molecular biology and genetics to complement ‘omics research. The overall goal of the training plan is to provide the PI with a solid foundation for continuing to investigate the genetic epidemiology of GERD in COPD and additional pulmonary diseases.

项目总结