Exploring the shared genetic architecture between periodontitis and cardiovascular disease

Area of Science:

• Genetics
• Cardiovascular Research
• Periodontology

Background:

• Epidemiological studies link periodontitis and cardiovascular diseases (CVD).
• Shared genetic mechanisms underlying this association are not well understood.
• This research aims to define the genetic architecture connecting periodontitis and CVD.

Purpose of the Study:

• To investigate bidirectional causal relationships between periodontitis and five CVD types.
• To identify shared genetic loci and genes contributing to both conditions.
• To explore the functional and biological pathways involved in their shared genetic basis.

Main Methods:

• Mendelian randomization (MR) using genome-wide association study (GWAS) summary data.
• Cross-trait analyses to assess genetic correlations and identify pleiotropic loci.
• Functional annotation, pathway analysis, and tissue-specificity analyses.

Main Results:

• No direct causal relationship found between periodontitis and CVD.
• Significant genetic correlation identified, supporting shared genomic architecture.
• Colocalization analysis revealed shared causal variants at specific loci (4p14, 15q25.1).
• Seven pleiotropic genes identified, including CD151, POLR2K, and HLA-DQA1.
• Shared genetic basis likely involves inflammation-metabolism regulatory axis.
• Pleiotropic signals enriched in immune and cardiovascular tissues.

Conclusions:

• A shared genetic basis exists between periodontitis and CVD.
• Potential mechanisms involve inflammation and cholesterol metabolism.
• Further studies with individual-level data are required to distinguish genetic from environmental factors.