GWAS for Periodontitis Phenotypes Using Multi-Ancestry All of Us Research Platform

Area of Science:

• Genetics
• Periodontology
• Bioinformatics

Background:

• Periodontitis is a complex inflammatory disease influenced by genetic and environmental factors.
• Understanding the genetic underpinnings of periodontitis is crucial for developing effective treatments.

Purpose of the Study:

• To perform a multi-ancestry genome-wide association study (GWAS) on periodontitis phenotypes stratified by stage, grade, and extent.
• To identify novel genetic loci associated with periodontitis using electronic health records (EHR) data.

Main Methods:

• Stratified periodontitis patients from the All of Us Research Program into clinically relevant phenotypes.
• Conducted ancestry-specific and multi-ancestry GWAS, comparing periodontitis patients to dental caries controls.
• Utilized EHR and genomic data from large-scale biobanks.

Main Results:

• Identified significant genetic associations (P<5×10^-8) at LINC00294 and CLMN loci for periodontitis grade in the African ancestry population.
• Discovered the XYLT1 locus associated with periodontitis grade in the Admixed American population.
• Found significant loci including RABGAP1L, DCHS2, and OSTM1 associated with periodontitis in the Admixed American population compared to dental caries.

Conclusions:

• Integrating EHR and genomic data enables informative dental phenotyping and discovery of novel molecular insights into periodontal disease.
• Genetic findings highlight potential targets for personalized periodontitis treatment strategies.
• The study underscores the value of large-scale biobanks for advancing dental research.