The Genetic Causal Association between Educational Attainment and Risk of 12 Common Musculoskeletal Disorders: A Two‐Sample Mendelian Randomization

Abstract

Objective

In numerous observational studies, there has been an indication that educational attainment (EA) can impact the intensity of pain and disability resulting from chronic musculoskeletal disorders. Nonetheless, the association observed in these studies is not entirely conclusive. The aim of this study was to investigate the genetic causal relationship between educational attainment and 12 musculoskeletal disorders using Mendelian randomization (MR).

Methods

The meta‐analysis of genome‐wide association studies (GWAS) identified 3952 single‐nucleotide polymorphisms (SNPs) associated with educational attainment (EA) from the Social Science Genetic Association Consortium (SSGAC). Genetic data for 12 musculoskeletal disorders, including osteonecrosis, osteoporosis, osteomyelitis, low back pain, gout, spinal stenosis, rheumatoid arthritis, meniscus derangement, rotator cuff syndrome, ankylosing spondylitis, cervicobrachial syndrome, and lateral epicondylitis, were obtained from the FinnGen consortium. We conducted a two‐sample Mendelian randomization analysis to examine the causal effect of EA on the risk of these musculoskeletal disorders using the TwoSampleMR package in R.

Results

Based on the inverse‐variance weighted (IVW) method, we found that a genetically predicted per standard deviation (SD) increase in EA was inversely associated with low back pain [odds ratio (OR) 0.46, 95% confidence interval (Cl) 0.51–0.61, p < 0.001], spinal stenosis (OR 0.62, 95% Cl 0.54–0.71, p < 0.001), rheumatoid arthritis (OR 0.65, 95% Cl 0.55–0.76, p < 0.001), meniscus derangement (OR 0.73, 95% Cl 0.65–0.82, p < 0.001), rotator cuff syndrome (OR 0.55, 95% Cl 0.49–0.61, p < 0.001), cervicobrachial syndrome (OR 0.50, 95% Cl 0.42–0.60, p < 0.001), and lateral epicondylitis (OR 0.30, 95% Cl 0.24–0.37, p < 0.001). There was no causal association between EA and osteonecrosis (OR 1.11, 95% CI 0.76–1.72, p = 0.60), osteoporosis (OR 0.91, 95% CI 0.65–1.27, p = 0.59), or osteomyelitis (OR 0.90, 95% CI 0.75–1.01, p = 0.22). Genetic predisposition to EA had a suggestive causal association with gout (OR 0.80, 95% CI 0.68–0.95, p = 0.01) and ankylosing spondylitis (OR 0.64, 95% CI 0.45–0.91, p = 0.01) after Bonferroni correction. None of the analyses revealed any horizontal pleiotropy or heterogeneity.

Conclusion

In our investigation, we have uncovered evidence supporting a causal relationship between low level of EA and the incidence of certain musculoskeletal disorders. In the future, it is imperative to ascertain risk factors such as lifestyle patterns linked with EA to uncover the underlying causal relationship and offer informed interventions for individuals.

Abstract

The overview of mendelian randomization design in the study. SSGAC, Social Science Genetic Association Consortium; GWAS, Genome‐wide association meta‐analysis; IVs, instrumental variables; LD, Linkage disequilibrium; SNP, Single Nucleotide Polymorphism.