Sources of bias in genomics research of oral and dental traits.

Evidence regarding the genomic basis of oral/dental traits and diseases is a fundamental pillar of the emerging notion of precision health. During the last decade, technological advances have improved the feasibility and affordability of conducting genome-wide association studies (GWAS) and studying the associations of emanating data with both common and rare oral conditions. Most evidence thus far emanates from GWAS of dental caries and periodontal disease that have tested the associations of several million single nucleotide polymorphisms (SNPs) with typically binary, health vs. disease phenotypes. GWAS offer advantages over the previous candidate-gene studies, mainly owing to their agnostic (i.e., unbiased, or hypothesis-free) nature. Nevertheless, GWAS are prone to virtually all sources of random and systematic error. Here, we review common sources of bias in genomics research with focus on GWAS including: type I and II errors, population stratification and heterogeneity, selection bias, adjustment for heritable covariates, appropriate reference panels for imputation, and gene annotation. We argue that valid and precise phenotype measurement is a key requirement, as GWAS sample sizes and thus statistical power increase. Finally, we stress that the lack of diversity of populations with phenotypes and genotypes is a major limitation for the generalizability and ultimate translation of the emerging genomics evidence-base into oral health promotion for all.