Advances in the application of Mendelian randomization in causal inference of periodontal diseases

YU Yang; WANG Yi; PAN Yi-huai

doi:10.19538/j.kq.2025.05.019

Abstract：Mendelian randomization(MR)is an analytical approach that utilizes genetic variants as instrumental vari-ables to assess causal relationships between exposures and outcomes.Its core principle is to leverage the random alloca-tion of genetic variants during gamete formation,effectively mitigating confounding factors,reverse causation,and mea-surement errors inherent in traditional observational studies,thereby enhancing the reliability of causal inference.Peri-odontal disease,as a multifactorial-mediated chronic inflammatory condition,relies predominantly on epidemiological observational studies to identify risk factors(e.g.,obesity,metabolic disorders),yet such methods struggle to establish de-finitive causal links.Furthermore,evidence regarding the impact of periodontal disease on systemic conditions(e.g.,car-diovascular diseases,diabetes)exhibits heterogeneity,and the reproducibility of conclusions remains incompletely estab-lished.Consequently,MR provides a novel causal inference paradigm for periodontal research,demonstrating unique ad-vantages,particularly in elucidating bidirectional associations between periodontal diseases and systemic disorders.This review summarizes the advances in MR applications in periodontology,encompassing studies on pathogenic mechanisms,risk factor analyses,and systemic implications of periodontal diseases.Nevertheless,MR findings still require validation through triangulation of multiple evidence sources(e.g.,experimental verification,prospective cohort studies)to strength-en robustness of conclusions.Future research should optimize instrumental variable selection,expand sample sizes,and integrate multi-omics data to deepen mechanistic exploration,thereby providing a theoretical foundation for precision prevention/control and interdisciplinary intervention of periodontal diseases.