Supplementary Material for: Genome-wide association studies on dental caries: A systematic review

Introduction Dental caries is a complex, multifactorial pathological disease. Despite advances in dental care, dental caries continues to pose a significant public health challenge. In addition to the behavioural factors (e.g. sugar exposure) and environmental / oral hygiene factors (e.g. fluoridate exposure in water and/or toothpaste) on the development of dental caries, potential genetic influence on dental caries susceptibility is possible but evidence is inconclusive, especially from a candidate gene approach. Over the past two decades, a genome-wide association study (GWAS) approach has also been applied to understand the genetic variants associated with dental caries. This study aims to systematically review GWAS on dental caries and identify relevant genetic risk variants of dental caries. Methods A systematic search was conducted on five databases (PubMed; ScienceDirect; EMBASE, GLOBAL HEALTH, MEDLINE) and one GWAS registry: GWAS Catalog in March 2024. Studies published after 2005 using GWAS approach were eligible. Q-genie tool was used for the quality assessment. Study information and single nucleotide polymorphisms (SNPs) at conventional (5x10-8) or suggestive (5x10-6) GWAS significance level were extracted and synthesized. Results A total of 16 papers were included, identifying 20 risk SNPs associated with dental caries at conventional GWAS significance level, and 33 SNPs at suggestive level. No common conventional SNPs or shared gene regions were found between studies. Of these studies, the sample sizes in majority were relatively small and only one study reported all recommended quality control steps. Most studies focused on the White or European-American population and dental caries on permanent teeth. In addition, some data resources were used repeatedly in multiple studies, particularly the Center for Oral Health Research in Appalachia cohorts (COHRA) which was used in 9 studies. Conclusion This study explored the GWAS on dental caries and summarized the heterogeneities of the included studies leading to inconsistent results. Guideline and more GWAS with larger sample size and multi-ethnicities are needed to fully understand the genetic basis of dental caries.