Causal relationship between thyroid dysfunction and hallux valgus: A two-sample Mendelian randomization study

Area of Science:

• Medical Genetics
• Endocrinology
• Orthopedics

Background:

• Observational studies suggest a link between thyroid dysfunction and hallux valgus (HV).
• The causal relationship between thyroid dysfunction and HV remains unclear.
• Thyroid hormones play a crucial role in various bodily functions, potentially influencing musculoskeletal health.

Purpose of the Study:

• To investigate the potential causal effect of thyroid dysfunction on hallux valgus (HV) using a two-sample Mendelian randomization (MR) approach.
• To determine if specific thyroid conditions, such as hypothyroidism and hyperthyroidism, are genetically linked to HV.
• To assess the genetic association of thyroid hormone levels (free thyroxine and TSH) with HV.

Main Methods:

• A two-sample Mendelian randomization (MR) study utilizing publicly available genome-wide association study (GWAS) data.
• Exposures included hypothyroidism, hyperthyroidism, free thyroxine (FT4), and thyrotropin (TSH), with single nucleotide polymorphisms (SNPs) sourced from large-scale GWAS.
• Hallux valgus (HV) served as the outcome, with associated SNPs obtained from a comprehensive GWAS; inverse variance weighted (IVW) method was primary, supported by sensitivity analyses.

Main Results:

• A significant causal effect of hypothyroidism on hallux valgus (HV) was identified, indicating hypothyroidism increases HV incidence (OR = 2.838, p = 0.028).
• No significant causal relationships were found between hyperthyroidism, FT4, or TSH and hallux valgus (p > 0.05).
• Sensitivity analyses confirmed the robustness and reliability of the findings, with no evidence of horizontal pleiotropy.

Conclusions:

• The study provides strong genetic evidence supporting a causal link between hypothyroidism and an increased risk of developing hallux valgus (HV).
• These findings highlight the importance of monitoring for HV in individuals with hypothyroidism.
• The results suggest potential for early prediction, prevention, and intervention strategies for hallux valgus in hypothyroid patients.