The Causal Relationship Between Hallux Valgus and Flatfoot ：A Mendelian Randomization Study

Aim: This research aimed to explore the potential causal link between hallux valgus(HV)and flatfoot. Approach: We conducted a two-sample Mendelian randomization(MR)analysis employing inverse-variance weighted(IVW)，weighted median，and MR-Egger regression methods.For the exposure variable，we utilized publicly available summary statistics from genome-wide association studies(GWAS)on HV(total n = 155，757;cases = 8，536，controls = 147，221)，while a GWAS on flatfoot(total n = 148，480;cases = 1，259，controls = 147，221)was used as the outcome measure. Findings: We identified eight single nucleotide polymorphisms(SNPs)that reached genome-wide significance from GWAS related to HV，which were utilized as instrumental variables（IVs）.The IVW method indicated a causal link between HV and flatfoot，yielding a beta coefficient of 0.410，a standard error(SE)of 0.197，and a p-value of 0.037. Conversely，MR-Egger regression suggested that directional pleiotropy was unlikely to skew the findings(intercept =-0.099，p = 0.522)，however，it did not establish a causal relationship between HV and flatfoot，presenting a beta of 1.077，SE of 1.003，and p = 0.324. Furthermore, the weighted median method indicated no causal relationship between HV and flatfoot, with a beta of 0.290, SE of 0.198, and p = 0.143. Conclusion: MR analysis suggests a potential causal link between HV and a heightened likelihood of developing flatfoot.