Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.
ABSTRACT: BACKGROUND:Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. METHODS:A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n?=?2314) or 'no deformity' (n?=?3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. RESULTS:We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR?=?0.48, p?=?2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. CONCLUSION:In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology.
Project description:BACKGROUND: The severity of hallux valgus is easily appreciated by its clinical appearance, however x-ray measurements are also frequently used to evaluate the condition, particularly if surgery is being considered. There have been few large studies that have assessed the validity of these x-ray observations across a wide spectrum of the deformity. In addition, no studies have specifically focused on older people where the progression of the disorder has largely ceased. Therefore, this study aimed to explore relationships between relevant x-ray observations with respect to hallux valgus severity in older people. METHODS: This study utilised 402 x-rays of 201 participants (74 men and 127 women) aged 65 to 94 years. All participants were graded using the Manchester Scale - a simple, validated system to grade the severity of hallux valgus - prior to radiographic assessment. A total of 19 hallux valgus-related x-ray observations were performed on each set of x-rays. These measurements were then correlated with the Manchester Scale scores. RESULTS: Strong, positive correlations were identified between the severity of hallux valgus and the hallux abductus angle, the proximal articular set angle, the sesamoid position and congruency of the first metatarsophalangeal joint. As hallux valgus severity increased, so did the frequency of radiographic osteoarthritis of the first metatarsophalangeal joint and a round first metatarsal head. A strong linear relationship between increased relative length of the first metatarsal and increased severity of hallux valgus was also observed. CONCLUSIONS: Strong associations are evident between the clinical appearance of hallux valgus and a number of hallux valgus-related x-ray observations indicative of structural deformity and joint degeneration. As it is unlikely that metatarsal length increases as a result of hallux valgus deformity, increased length of the first metatarsal relative to the second metatarsal may be a contributing factor to the development and/or progression of hallux valgus.
Project description:Hallux valgus is a serious medical concern for classical ballet dancers. Although it is well-known that progression of hallux valgus is related to inappropriate movement techniques in classical ballet, the kinematic relationship between the degree of hallux valgus and ballet techniques has not been substantiated. To develop proper training methods that prevent progression of hallux valgus, this study aimed to investigate the relationship between the degree of hallux valgus and movement techniques in classical ballet. Seventeen female classical ballet dancers at the advanced college-level participated in this study. Kinematic analysis of standing and plié in the first position was conducted via video capture technique. The Pearson product-moment correlation analysis was performed to examine the degree of hallux valgus and the following three kinematic variables: (1) the extent to which turnout is forced by other joints in the lower extremity than the hip joint, (2) the direction difference between the knee and toe in the transverse plane, and (3) the pelvis obliquity angle. Among these kinematic variables, we found a significant correlation between the hallux valgus angle and the pelvis obliquity angle during plié (P = .045). The greater the hallux valgus angle, the greater the retroversion of the pelvis, a result which was contrary to our prediction. We present the first evidence that the degree of hallux valgus correlates with kinematics in a very basic technique of classical ballet.
Project description:The aim of this study was to confirm whether the length of the first metatarsal and the length of the hallux are greater than normal in the initial phase of the hallux valgus deformity. In a sample of 152 radiographs (98 of normal feet and 54 of incipient hallux valgus feet), the length of the first metatarsal and the hallux was measured according to methods previously described. Comparisons were made between normal and hallux valgus feet, and between male and female feet. The results show significant differences between the two groups in the first metatarsal (P<0.0001) and hallux (P<0.001). In the male feet, these differences are more marked (when comparing the length of the hallux between the female hallux valgus feet and the female normal feet, P>0.05). This indicates that in men with hallux valgus, the excess in length of the first metatarso-digital segment is greater than in women that develop this deformity, at least in its initial phase. According to these results, the size of the first metatarso-digital segment could be involved in the development of the hallux valgus deformity.
Project description:A total of 118 feet with Hallux valgus and Hallux rigidus treated by the Keller-Brandes method were re-examined clinically and radiologically after 9.1 years (range: 1.7-24.3). Correction of the Hallux valgus angle was obtained from an average of 40 degrees to 23 degrees in the Hallux valgus group. Improvement in the postoperative range of motion was observed when the aftertreatment consisted of Kirschner-wire distraction instead of an axial Kirschner-wire transfixation. The patients who underwent Keller-Brandes surgery for Hallux valgus had less pain when the aftertreatment was carried out using an axial Kirschner wire, while those operated on for Hallux rigidus had less pain when the aftertreatment consisted of distraction. The percentage of satisfied or very satisfied patients with the cosmetic results of the Keller-Brandes arthroplasty was more than 66.7%. Patients with Hallux valgus and postoperative aftertreatment with Kirschner wire transfixation were the most satisfied patients, while patients with Hallux rigidus were very satisfied with the postoperative distraction. Our good results are comparable to those in other studies and confirm the success of the Keller-Brandes resection arthroplasty in Hallux valgus with osteoarthritis of the first metatarsophalangeal joint in older patients whose demand for movement is less, and in Hallux rigidus in less active older patients.
Project description:Hallux valgus (HV) affects ?36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV.HV was assessed in three Caucasian cohorts (n=2263, n=915 and n=1231 participants, respectively). In each cohort, a GWAS was conducted using 2.5?M imputed SNPs. Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327).The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV were sex specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=0.000000546×10(-7)); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=0.000000721×10(-7)). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p value =0.0000000041×10(-9)). The association signals diminished when combining men and women.The findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation.
Project description:BACKGROUND:The aim of the study was to evaluate changes in plantar pressure distribution in feet affected by hallux valgus compared with their contralateral non-affected feet and with the feet of healthy control subjects. METHODS:Thirty-six patients with unilateral hallux valgus who were indicated for surgery and 30 healthy subjects were assessed on a pedobarographic instrumented treadmill for step length and width, mean stance phase, and plantar foot pressure distribution. Plantar pressure distribution was divided into eight regions. RESULTS:Significantly higher plantar pressures were observed in hallux valgus feet under the second and third metatarsal heads (p =?.033) and the fourth and fifth toes (p <?.001) than in the healthy control feet. Although decreased pressures were measured under the hallux in affected feet (197 [82-467] kPa) in contrast to the contralateral side (221 [89-514] kPa), this difference failed to reach statistical significance (p =?.055). The gait parameters step width, step length, and single-limb support did not show any differences between hallux valgus and control feet. CONCLUSION:Although the literature on changes in plantar pressures in hallux valgus remains divided, our findings on transferring load from the painful medial to the central and lateral forefoot region are consistent with the development of transfer metatarsalgia in patients with hallux valgus.
Project description:Quantitative analyses of plantar pressure images typically occur at the group level and under the assumption that individuals within each group display homogeneous pressure patterns. When this assumption does not hold, a personalized analysis technique is required. Yet, existing personalized plantar pressure analysis techniques work at the image level, leading to results that can be unintuitive and difficult to interpret. To address these limitations, we introduce PAPPI: the Personalized Analysis of Plantar Pressure Images. PAPPI is built around the statistical modelling of the relationship between plantar pressures in healthy controls and their demographic characteristics. This statistical model then serves as the healthy baseline to which an individual's real plantar pressures are compared using statistical parametric mapping. As a proof-of-concept, we evaluated PAPPI on a cohort of 50 hallux valgus patients. PAPPI showed that plantar pressures from hallux valgus patients did not have a single, homogeneous pattern, but instead, 5 abnormal pressure patterns were observed in sections of this population. When comparing these patterns to foot pain scores (i.e. Foot Function Index, Manchester-Oxford Foot Questionnaire) and radiographic hallux angle measurements, we observed that patients with increased pressure under metatarsal 1 reported less foot pain than other patients in the cohort, while patients with abnormal pressures in the heel showed more severe hallux valgus angles and more foot pain. Also, incidences of pes planus were higher in our hallux valgus cohort compared to the modelled healthy controls. PAPPI helped to clarify recent discrepancies in group-level plantar pressure studies and showed its unique ability to produce quantitative, interpretable, and personalized analyses for plantar pressure images.
Project description:BACKGROUND:It is still unknown whether the excessive length of the first ray is a risk factor for hallux valgus recurrence. The purpose of this study is to clarify the relationship between the excessive length of the first ray and the recurrence of hallux valgus. METHODS:Between 2008 and 2011, a total of 186 feet (left 105, right 81) who underwent chevron osteotomy combined with distal soft tissue procedure in our foot and ankle center were retrospectively reviewed. A postoperative hallux valgus angle(HVA) ?20° was defined as recurrence. Patients were divided into two groups: recurrence and non-recurrence group. Weight-bearing radiographs were evaluated preoperatively and at the time of last follow-up for both groups. Radiographic parameters including the length of the great toe(P1), the length of the second toe(P2), the length distance between the first and second metatarsal(D), the hallux valgus angle(HVA) were obtained. The excessive length of the first ray(EL) was calculated using the equation of EL = P1-P2-D. RESULTS:A total of 45 patients (24.2%) had hallux valgus recurrence at the time of last follow-up with a mean follow-up of 83.7 ±12.1 months (range, 66-110). The mean postoperative P1 was 5.06±0.39cm for recurrence group and 4.84±0.34cm for no recurrence group(p<0.001). The mean post operative EL was 5.71±5.01mm for recurrence group and 1.61±4.09mm for no recurrence group(p<0.001). The predictive cutoff value of postoperative P1 and postoperative EL for hallux valgus recurrence was 4.9cm [odds ratio (OR) = 8.67, p = 0.03] and 0.4cm (OR = 6.79, p = 0.001) respectively. CONCLUSIONS:Significant relationships between postoperative P1, postoperative EL and hallux valgus recurrence were identified according to our radiographic results. A postoperative P1>4.9cm and postoperative EL>0.4cm can be risk factors for hallux valgus recurrence. The appreciation of the excessive length of the first ray prior to surgery may help to improve the surgical outcome.
Project description:The underlying reason for recurrence of hallux valgus deformity after bunion surgery is multifactorial and includes surgeon-based and patient-based factors as well as original components of deformity initially unaddressed at the index procedure. Surgical treatment of a recurred hallux valgus deformity should be undertaken using the same guidelines for correction of a primary hallux valgus deformity. It requires correction of bony alignment, restoration of joint congruity, and achievement of soft tissue balance. The purpose of this Technical Note is to describe the details of endoscopic soft tissue procedure to correct a recurred hallux valgus deformity. To successfully complete this procedure, adequate lateral release to achieve soft tissue balance around the first metatarsophalangeal joint with reduction of the sesamoid bones is mandatory.
Project description:Arthrodesis of the first metatarsophalangeal joint is indicated for hallux valgus associated with degenerative changes, severe deformity, or rheumatoid arthritis and those for whom primary hallux valgus surgery has failed. Open approach requires extensive soft tissue dissection. The purpose of this Technical Note was to report the details of arthroscopic arthrodesis of the first metatarsophalangeal joint in severe and rigid hallux valgus deformity. This is a combination of endoscopic lateral release of the first metatarsophalangeal joint and arthroscopic arthrodesis of the joint. Endoscopic lateral release will convert the deformity into a flexible one and facilitate a subsequent arthrodesis procedure.