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Principal Investigator
Chuanwen Fan
Position Title
Associate Prof.
About this CDAS Project
PLCO (Learn more about this study)
Project ID
Initial CDAS Request Approval
Jun 24, 2022
A genome wide association study of Helicobacter pylori infection and the causal effect between Helicobacter pylori infection and digestive tract diseases
Helicobacter pylori (H. pylori) infection is the principal cause of peptic ulcer disease, gastritis, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. However, increasing evidence has shown that it may interfere with many biological processes and determine or influence the occurrence of many diseases outside the stomach. HP, therefore, is identified as a definite class 1 carcinogen by the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC). Eradication of H. pylori in patients and high-risk carriers remains the most successful method in preventing the development of gastric cancer and H. pylori-related diseases. H. pylori is present in roughly 50% of the human population worldwide, suggesting genetic susceptibility to H. pylori. Some individuals are never infected by H pylori, and others can clear the infection spontaneously when colonized. Moreover, only a small proportion of the H pylori–colonized population develop gastric cancer or organic disease, suggesting that host-specific factors governing the host-pathogen interactions are involved in disease risk. Although the host genetic background is suggested to be involved in the clinical outcome of H pylori infection in the previous study, it is necessary a better understanding of the genetic contributions to H. pylori infection and pathogenicity by using a more powerful data.
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.


Ben Zhang,
Xia Jiang,
Chenghan Xiao
Li Zhang
Mingshuang Tang
Yanna Shang
Stefan Weiss
Georg Homuth
Markus M. Lerch