Effect of interleukin-17 on periodontitis development: An instrumental variable analysis

Baumeister, Sebastian-Edgar; Holtfreter, Birte; Reckelkamm, Stefan Lars; Hagenfeld, Daniel; Kocher, Thomas; Alayash, Zoheir; Ehmke, Benjamin; Baurecht, Hansjörg; Nolde, Michael

Abstract

Background: Circulating levels of interleukin-17 (IL-17) are associated with the presence and severity of periodontitis. However, whether IL-17 is causal for disease development is unknown. We investigated the effect of genetically proxied IL-17 on periodontitis using instrumental variable analysis. Methods: We identified 12 genetic variants from genome-wide association study (GWAS) of 7760 European descent individuals, used these variants as instrumental variables for IL-17, and linked them to a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Generalized weighted least squares analysis accounted for linkage disequilibrium of variants. Results: We found an inverse association of genetically proxied IL-17 and periodontitis (odds ratio, 0.84; 95% confidence interval: 0.75‒0.94; p = 0.003), which was corroborated after sensitivity analysis for horizontal pleiotropy. Conclusion: The findings suggest that IL-17 protects against initial periodontitis.