Bidirectional causal relationship between psychiatric disorders and osteoarthritis: A univariate and multivariate Mendelian randomization study

Author:

Meng Jinzhi1,Cai Youran2,Yao Jun1,Yan Haiwei3ORCID

Affiliation:

1. Bone and Joint Surgery The First Affiliated Hospital of Guangxi Medical University Nanning China

2. Department of Ophthalmology The First Affiliated Hospital of Guangxi Medical University Nanning China

3. Department of Sports Medicine The Fourth Affiliated Hospital of Guangxi Medical University Liuzhou China

Abstract

AbstractBackgroundObservational studies have shown associations between psychiatric disorders and osteoarthritis (OA). However, the causal impact of different psychiatric disorder types on specific sites of osteoarthritis remains unclear. This study aimed to comprehensively understand the potential causal associations between psychiatric disorders and osteoarthritis using Mendelian randomization (MR) analysis.MethodsWe collected data from genome‐wide association studies of knee osteoarthritis (KOA) (n = 403,124), hip osteoarthritis (HOA) (n = 393,873), osteoarthritis of the knee or hip (KHOA) (n = 417,596), as well as three psychiatric disorders: bipolar disorder (n = 41,917), major depressive disorder (n = 170,756), and schizophrenia (n = 76,755) among European populations. We applied bidirectional univariate and multivariate MR analyses, including inverse variance weighted, Mendelian randomization‐Egger, weighted median, simple mode, and weighted mode. We considered p < .05 as a criterion for identifying potential evidence of association. Bonferroni correction was used for multiple tests.ResultsOur univariate MR analysis results demonstrated that bipolar disorder is a protective factor for KOA (OR = 0.90, 95% CI = 0.83 to 0.97, p = 0.0048) and may also be protective for KHOA (p = 0.02). Conversely, major depression has a positive causal effect on both KOA (OR = 1.27; 95% CI = 1.08 to 1.49; p = 0.0036) and KHOA (OR = 1.24; 95% CI = 1.12 to 1.37; p = 3.62×10‐05). Furthermore, our analysis suggested that KHOA may be a risk factor for major depression (OR = 1.06; 95% CI = 1.00 to 1.12; p = 0.0469) in reverse MR. After adjusting smoking (OR = 1.46; 95% CI = 1.19 to 1.65; p = 0.0032) and body mass index (OR = 1.44; 95% CI = 1.09 to 1.81; p = 8.56×10‐04), the casual association between major depression and KHOA remained.ConclusionOur study indicates that major depression is a great risk factor for KHOA, increasing the likelihood of their occurrence. However, further in‐depth studies will be required to validate these results and elucidate the underlying molecular mechanisms.

Publisher

Wiley

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