Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple...

Area of Science:

• Environmental Health
• Genomics
• Toxicology

Background:

• Chemical elements play a crucial role in human health.
• Genomic data for complex diseases provide opportunities to study element-disease relationships.
• Gene set enrichment analysis (GSEA) is a valuable tool for investigating these connections.

Purpose of the Study:

• To systematically investigate associations between chemical elements and complex diseases/traits.
• To apply GSEA by integrating element-gene interaction data with genome-wide association study (GWAS) data.
• To identify both known and novel relationships between elements and diseases.

Main Methods:

• Extracted element-gene interaction data for 24 elements from the Comparative Toxicogenomics Database (CTD).
• Downloaded GWAS summary datasets for 24 complex diseases/traits from dbGaP or GEFOS.
• Applied GSEA to analyze integrated datasets and identify significant associations (False Discovery Rate < 0.05).

Main Results:

• Identified significant associations between 7 elements and 13 complex diseases/traits.
• Confirmed known links, including aluminum with Alzheimer's disease and calcium with bone mineral density.
• Discovered novel associations, such as nickel with hypertriglyceridemia and bipolar disorder.

Conclusions:

• The study validates the effectiveness of GSEA in uncovering element-disease relationships.
• Findings provide novel clues for discovering causal links between elements and complex diseases.
• Results support the integration of genomic and toxicogenomic data for health research.