Genetic Epidemiology of GERD in COPD - 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.