A genome wide association study of Helicobacter pylori infection and the causal effect between Helicobacter pylori infection and digestive tract diseases
PLCO is a large-scale prospective cohort study where data has been collected on many known H pylori-related diseases, including peptic ulcer disease, gastritis, gastric carcinoma, colorectal carcinoma, vitamin B12 deficiency, insulin resistance, and metabolic syndrome, diabetes mellitus, and non-alcoholic liver disease. Importantly, H pylori infection and genotyping also have been examined in PLCO. Thus, the availability of such data in the PLCO study gives us an opportunity to estimate the genetic susceptibility to H. pylori and develop a polygenic risk score for risk-prediction of H. pylori infection to develop diseases. We are proposing to conduct a genome-wide association study including all PLCO participants with available genetic and H. pylori infection data (H. pylori antigens, C13 and anti–H pylori serologic antibody). We are requesting genetic and H. pylori infection data as well as demographic, and lifestyle data and H. pylori infection-related diseases (peptic ulcer disease, gastritis, gastric carcinoma, colorectal carcinoma, vitamin B12 deficiency, or serum level of vitamin B12, insulin resistance, metabolic syndrome, diabetes mellitus, and non-alcoholic liver disease) for potential confounder adjustment.
Aim 1: To identify genetic variants associated with individual H. pylori infection in the PLCO cohort.
Aim 2: To develop genetic instruments for H. pylori infection for Mendelian Randomization (MR) analyses.
Aim 3: To investigate the causal effect of H. pylori and H. pylori infection-related diseases, especially digestive tract diseases.
Markus M. Lerch