Mendelian Randomization Rules Out Causation Between Periodontitis and Hand Grip Strength

Abstract Background: Periodontitis (PD) has been linked to low hand grip strength in previous epidemiological observational studies; however, the results are inconclusive. The purpose of this study was to investigate the causal association of PD with hand grip strength. Methods: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied three complementary methods, including weighted median, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. Due to multiple testing, associations with p values < .016 were considered as statistically significant, and p values ≥ .016 and < .05 were considered as suggestively significant. Besides, a multivariable MR (MVMR) design was carried to adjust for body mass index (BMI) and type 2 diabetes (T2D) as well. Results: Generally, PD and one of subtypes-Aggressive Periodontitis (AgP) might not affect the risk of low hand grip strength (beta = 0.117 [-0.064, 0.298], beta = -0.018 [-0.042, 0.006]). However, genetically-elevated risk of Chronic Periodontitis (CP) might cause lower hand grip strength (beta = 0.035, p-value = 0.023) while turning insignificant at Bonferroni correction. Besides, no causal effect of hand grip strength on PD and CP was observed (OR = 0.987 [0.964, 1.009]). MVMR analysis also supported such null associations even after adjusting for BMI and T2D. Conclusion: This MR study ruled out the causal relationship between PD and hand grip strength, despite observational studies reporting an association between PD and hand grip strength.