Unraveling the genetic association between obesity-related anthropometric indices and foot deformities in the European population: A two-sample Mendelian randomization study

Obesity and foot deformities pose substantial public health burdens globally. However, their causal relationship remains uncertain due to confounding and reverse causation in observational studies. This study aimed to investigate causal associations between obesity-related anthropometric indices and foot deformities using Mendelian randomization (MR) analysis. This two-sample MR study utilized genetic instruments from publicly available genome-wide association studies databases. We extracted single nucleotide polymorphisms (SNPs) as instrumental variables for obesity (6 SNPs), body mass index (372 SNPs), waist circumference (257 SNPs), and hip circumference (313 SNPs). The outcomes included flat foot and hallux valgus from the FinnGen Biobank. Inverse variance weighted method was used as the primary analysis, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses included heterogeneity tests and pleiotropy assessments. Genetically predicted obesity showed significant causal effects on flat foot (odds ratio [OR]: 1.516, 95% confidence interval [CI]: 1.166-1.970, P = .002) and hallux valgus (OR: 1.179, 95% CI: 1.041-1.336, P = .010). Similar associations were observed for body mass index (flat foot: OR: 1.798, 95% CI: 1.491-2.168, P < .001; hallux valgus: OR: 1.193, 95% CI: 1.075-1.324, P = .001), waist circumference (flat foot: OR: 1.542, 95% CI: 1.210-1.966, P < .001; hallux valgus: OR: 1.270, 95% CI: 1.108-1.456, P = .001), and hip circumference (flat foot: OR: 1.380, 95% CI: 1.134-1.680, P = .001; hallux valgus: OR: 1.154, 95% CI: 1.009-1.319, P = .036). This genetic study provides strong evidence supporting causal relationships between obesity-related anthropometric indices and foot deformities. These findings emphasize the importance of weight management in preventing foot deformities and suggest potential therapeutic targets for intervention strategies.