High Heritability of Hallux Valgus and Lesser Toe Deformities in Adult Men and Women

Abstract

Objective To estimate heritability of three common disorders affecting the forefoot: hallux valgus, lesser toe deformities and plantar forefoot soft tissue atrophy in adult Caucasian men and women. Methods Between 2002-2008, a trained examiner used a validated foot exam to document presence of hallux valgus, lesser toe deformities and plantar soft tissue atrophy in 2,446 adults from the Framingham Foot Study. Among these, 1,370 participants with available pedigree structure were included. Heritability (h2) was estimated using pedigree structures by Sequential Oligogenic Linkage Analysis Routines (SOLAR) package. Results were adjusted for age, sex and BMI. Results Mean age of participants was 66 years (range 39 to 99 years) and 57% were female. Prevalence of hallux valgus, lesser toe deformities and plantar soft tissue atrophy was 31%, 29.6% and 28.4%, respectively. Significant h2 was found for hallux valgus (0.29 ~ 0.89, depending on age and sex) and lesser toe deformity (0.49 ~ 0.90 depending on age and sex). The h2 for lesser toe deformity in men and women aged 70+ years was 0.65 (p= 9×10−7). Significant h2 was found for plantar soft tissue atrophy in men and women aged 70+ years (h2 = 0.37; p=3.8×10−3). Conclusion To our knowledge, these are the first findings of heritability of foot disorders in humans, and they confirm the widely-held view that hallux valgus and lesser toe deformities are highly heritable in European-descent Caucasian men and women, underscoring the importance of future work to identify genetic determinants of the underlying genetic susceptibility to these common foot disorders.

Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans

“…HV is one of the most common foot disorders in older Caucasian and African Americans2 8 and has been confirmed to be heritable in our recent publication 16. In this first ever GWAS meta-analysis of HV, we report a set of potentially suggestive SNPs with p values less than 5×10 −6 in male-specific and female-specific analyses.…”

“…Pedigree studies have found that 63–90% of individuals with HV report a family history of the condition 13–15. More recently, HV was found to be highly heritable in the Framingham Heart Study (FHS)16 (involving 1370 European descent Caucasian participants from 429 families) and the Korean Healthy Twin Study (involving 1265 East Asian participants and 206 twin pairs) 17. Although these studies suggest that HV may be hereditary, no candidate gene association study or genome-wide association study (GWAS) has been conducted to examine the genetic predisposition of HV.…”

Genetic Influences on Hallux Valgus in Koreans: The Healthy Twin Study

“…Considering that most of the study participants in the Korean study comprised those aged between age 39 and 60, the two findings are generally compatible in indicating the importance of genetic contributions to HV deformity. When we further analyzed our data using the same cut-off as was used by Hannan et al (2013;HVA >15 degrees), the heritability estimate increased to 0.63. There could be some possible explanations for this difference of between 0.45 and 0.63.…”

“…Because the relatives of clinical cases share gene pools that predispose an increased risk of HV, the heritability of 0.63 might be overestimated. A recent report by Hannan et al (2013), which adopted the criteria of HVA over 15 degrees as determining HV, demonstrated that the overall heritability in a US white population was 0.29, and heritability was increased to 0.45 when it was estimated for those aged between 39 and 60 years. The same study showed that overall heritability of lesser toe deformity was estimated to be 0.54.…”

“…Previous studies about the etiology of HV, however, were mostly based on clinical cases, which are subject to selection bias unless the ascertainment of cases are not corrected properly (Hardy & Clapham, 1951;Pique-Vidal et al, 2007), and the definition of HV relied on questionnaires, except a recent study that included radiologic examinations in a general population (Hannan et al, 2013).…”