Causal relationship between molecular markers of biological aging and orthopedic diseases: A two-sample bidirectional Mendelian randomization study

Abstract

Background

Studies indicate an association between biological aging and orthopedic diseases, but the causality remains unclear.

Aims

This study aims to investigate the bidirectional causal relationship between molecular markers of biological aging age and orthopedic conditions.

Methods

A two-sample Mendelian randomization (MR) analysis based on a genome-wide association study (GWAS) was conducted to explore these causal relationships. Analysis methods included inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode. Sensitivity analyses involved Cochran's Q, MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO) tests.

Results

The forward MR analysis identified several causal relationships: granulocyte proportions influenced intervertebral disc degeneration (IVDD) (OR 0.2316, P = 0.0101) and low back pain (LBP) (OR 0.2624, P = 0.007); telomere length (TL) affected cervical spondylosis (C/S) (OR 0.8759, P = 0.0167) and IVDD (OR 0.9184, P = 0.023); fibroblast growth factor-23 (FGF-23) impacted frozen shoulder (FS) (OR 1.2424, P = 0.0316); and HannumAge influenced C/S (OR 0.9518, P = 0.0233). The reverse MR analysis found that FS influenced TL (OR 0.9582, P = 0.0002) and α-Klotho (OR 0.7592, P = 0.0256), while sciatica affected TL (OR 0.9344, P = 0.0055) and C/S impacted PhenoAge (OR 1.6583, P = 0.0131) after outlier exclusion. Cochran's Q indicated heterogeneity in certain analyses, and MR-Egger showed no horizontal pleiotropy in significant causal associations.

Conclusions

This study suggests a potential causal associations between molecular markers of biological aging and orthopedic diseases, suggesting avenues for future research into the underlying mechanisms.