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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1434602

A Mendelian Randomization Study of the Association between Serum Uric Acid and Osteoporosis Risk

Provisionally accepted
Heng Wu Heng Wu 1Hairui Li Hairui Li 2Xiao Dai Xiao Dai 1Yu Dai Yu Dai 2Hao Liu Hao Liu 1Shuang Xu Shuang Xu 1Jinbang Huang Jinbang Huang 2Hao Chi Hao Chi 2Song Wang Song Wang 1*
  • 1 Department of Orthopedics, the Affiliated Hospital of Southwest Medical University Luzhou 646000, China, Luzhou, China
  • 2 Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan Province, China

The final, formatted version of the article will be published soon.

    The relationship between serum uric acid (SUA) and osteoporosis (OP) has yielded conflicting results in observational studies. This Mendelian randomization (MR) study aims to elucidate the causal association between SUA and OP.A two-sample MR analysis was conducted using summary-level data from genome-wide association studies (GWAS). Two sets of polygenic instruments strongly associated (p < 5 × 10-8) with SUA were extracted from the CKDGen consortium and UK biobank. Polygenic instruments associated with OP (p < 5 × 10-8) were derived from FinnGen biobank and UK biobank. Inverse variance weighting (IVW) was employed as the primary analysis method. Additionally, we utilized MR-Egger, weighted median, the simple mode method, and the weighted mode as complementary analyses. Cochran's Q statistics were used to assess heterogeneity, with MR-Egger intercept testing and MR pleiotropy residual sum and outlier (MR-PRESSO) to examine horizontal pleiotropy. Sensitivity analysis was performed using the leave-one-out method.The IVW analysis conducted across four groups confirms no significant causal relationship between SUA concentration and OP: UKB-UKB (OR: 1.001, 95% CI: 0.999-1.003, p=0.464), CKD-UKB (OR: 1.001, 95% CI: 0.999-1.003, p=0.349), UKB-Fin (OR: 0.934, 95% CI: 0.747-1.168, p=0.549), CKD-Fin (OR: 1.041, 95%CI: 0.934-1.161, p=0.470). Furthermore, additional four MR analyses corroborated these findings. Upon excluding all outliers identified by the MR-PRESSO test, no significant directional pleiotropy was observed, except for some data heterogeneity noted in the UKB-UKB group (Q=50.65, P=0.002). Additionally, a leave-one-out analysis indicated that no single SNP exerted undue influence on the results.This MR analysis provides convincing genetic evidence that there is no causal association between SUA and OP, SUA is unlikely to increase or reduce the risk of OP.

    Keywords: Serum uric acid, Osteoporosis, genetic, casual effect, Mendelian randomization

    Received: 18 May 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Wu, Li, Dai, Dai, Liu, Xu, Huang, Chi and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Song Wang, Department of Orthopedics, the Affiliated Hospital of Southwest Medical University Luzhou 646000, China, Luzhou, China

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