A Trace Element-Ulcer Map: Decoding Micronutrient-Ulcer Relationships Through Genetic Architecture and...

Area of Science:

• Genetics and Nutritional Epidemiology
• Investigating the complex interplay between trace elements and ulcer development across diverse anatomical locations.

Background:

• The relationship between circulating micronutrients and susceptibility to various ulcer types is not well understood.
• Existing research lacks a comprehensive map of trace element associations with different ulcer phenotypes.

Purpose of the Study:

• To construct a systematic trace element-ulcer map using advanced genetic and statistical methods.
• To identify specific micronutrients that influence the risk of developing different types of ulcers.

Main Methods:

• Utilized summary-level data from large-scale genome-wide association studies (GWAS) involving over 3 million individuals.
• Employed two-sample Mendelian randomization (MR), Causal Analysis Using Summary Effect estimates (CAUSE), and MR-Clust for robust analysis.
• Integrated genetic-instrumented inference, pleiotropy-aware modeling, and heterogeneity-sensitive clustering.

Main Results:

• Genetically elevated zinc levels were identified as a risk factor for gastric and esophageal ulcers.
• Iron showed a protective effect against gastric ulcers, and calcium against duodenal ulcers.
• Identified potential mechanistic heterogeneity in the vitamin C-corneal ulcer relationship.

Conclusions:

• Zinc is prioritized as a key candidate for further mechanistic research in gastric ulcer pathogenesis.
• The study provides a broad overview of trace element-ulcer relationships, highlighting specific associations.
• The developed integrative framework can guide future etiological research and nutritional interventions for ulcers.