AUTHOR=Huang Guiwu , Zhong Yanlin , Li Wenchang , Liao Weiming , Wu Peihui 

TITLE=Causal Relationship Between Parathyroid Hormone and the Risk of Osteoarthritis: A Mendelian Randomization Study

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.686939

DOI=10.3389/fgene.2021.686939

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Previous studies have demonstrated an inverse association between parathyroid hormone (PTH) and the risk of osteoarthritis (OA). However, it remains unknown whether such association reflects causality. We aimed to apply a Mendelian randomization (MR) approach to investigate the causal association between PTH and OA.</p></sec><sec><title>Materials and Methods</title><p>We performed a two-sample MR analysis using summary statistics from 13 cohorts (PTH, <italic>N</italic> = 29,155) and a recent genome-wide association study meta-analysis (OA, <italic>N</italic> = 455,221) by the UK Biobank and Arthritis Research UK OA Genetics (arcOGEN). MR analyses were carried out mainly using the inverse-variance-weighted method. Sensitivity analyses were performed to test the robustness of the associations using the weighted median method, the MR–Egger method, and “leave-one-out” analysis. Analyses were performed again to test whether the associations remained statistically significant after excluding any outlier variants that were detected using the MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) test.</p></sec><sec><title>Results</title><p>Five single-nucleotide polymorphisms (SNPs) were selected as instrumental variables at the genome-wide significance threshold (<italic>p</italic> &lt; 5 × 10<sup>–8</sup>). The causal effect between PTH and OA was genetically predicted using the inverse-variance-weighted method (odds ratio = 0.67, 95% confidence interval: 0.50–0.90; <italic>p</italic> = 0.008). This result was borne out using the weighted median method (odds ratio = 0.73, 95% confidence interval: 0.60–0.90; <italic>p</italic> = 0.004). The causality remained robust after discarding the outlier variants as well as SNPs associated with confounding factors.</p></sec><sec><title>Conclusion</title><p>MR analysis supported a potential causative relationship between decreased serum circulating PTH and a higher risk of hip and knee OA.</p></sec>