Assessment of Bidirectional Relationships Between Polycystic Ovary Syndrome and Periodontitis: Insights From a Mendelian Randomization Analysis

Pengfei Wu; Xinghao Zhang; Ping Zhou; Wan Zhang; Danyang Li; Mingming Lv; Xiaoyao Liao

doi:10.3389/fgene.2021.644101

Assessment of Bidirectional Relationships Between Polycystic Ovary Syndrome and Periodontitis: Insights From a Mendelian Randomization Analysis

Front Genet. 2021 Mar 26:12:644101. doi: 10.3389/fgene.2021.644101. eCollection 2021.

Authors

Pengfei Wu^{1

2}, Xinghao Zhang³, Ping Zhou³, Wan Zhang⁴, Danyang Li⁴, Mingming Lv^{5

6}, Xiaoyao Liao⁷

Affiliations

¹ Hunan Key Laboratory of Animal Models for Human Diseases, Department of Laboratory Animals, Third Xiangya Hospital, Central South University, Changsha, China.
² Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Center for Medical Genetics, Central South University, Changsha, China.
³ Department of Ultrasound, Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Biology, College of Arts and Sciences, Boston University, Boston, MA, United States.
⁵ Department of Oral Maxillofacial-Head Neck Oncology, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Shanghai Key Laboratory of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, Shanghai, China.
⁷ School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, United Kingdom.

Abstract

Background: Observational studies have indicated an association between polycystic ovary syndrome (PCOS) and periodontitis, but it is unclear whether the association is cofounded or causal. We conducted a two-sample Mendelian randomization (MR) study to investigate the bidirectional relationship between genetically predicted PCOS and periodontitis.

Methods: From two genome-wide association studies we selected 13 and 7 single nucleotide polymorphisms associated with PCOS and periodontitis, respectively, as instrumental variables. We utilized publicly shared summary-level statistics from European-ancestry cohorts. To explore the causal effect of PCOS on periodontitis, 12,289 cases of periodontitis and 22,326 controls were incorporated, while 4,890 cases of PCOS and 20,405 controls in the reverse MR. Inverse-variance weighted method was employed in the primary MR analysis and multiple sensitivity analyses were implemented.

Results: Genetically determined PCOS was not causally associated with risk of periodontitis (odds ratio 0.97; 95% confidence interval 0.88-1.06; P = 0.50) per one-unit increase in the log-odds ratio of periodontitis. Similarly, no causal effect of periodontitis on PCOS was shown with the odds ratio for PCOS was 1.17 (95% confidence interval 0.91-1.49; P = 0.21) per one-unit increase in the log-odds ratio of periodontitis. Consistent results were yielded via additional MR methods. Sensitivity analyses demonstrated no presence of horizontal pleiotropy or heterogeneity.

Conclusion: The bidirectional MR study couldn't provide convincing evidence for the causal relationship between genetic liability to PCOS and periodontitis in the Europeans. Triangulating evidence across further observational and genetic-epidemiological studies is necessary.

Keywords: Mendelian randomization; causal inference; genetic epidemiology; periodontitis; polycystic ovary syndrome.