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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.

SUBMITTER: Arbeeva L

PROVIDER: S-EPMC7057609 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

Arbeeva Liubov L Yau Michelle M Mitchell Braxton D BD Jackson Rebecca D RD Ryan Kathleen K Golightly Yvonne M YM Hannan Marian T MT Nelson Amanda A Jordan Joanne M JM Hochberg Marc C MC

Journal of foot and ankle research 20200304 1

<h4>Background</h4>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 ge ...[more]

PMID: 32131869

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Project description:BackgroundHallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender.MethodsElectronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model.ResultsA total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis.ConclusionsNotwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research.

Project description:BackgroundAlthough the etiology of hallux valgus is contested, in some patients it may be failure of the stabilizing soft tissue structures around the first ray of the foot. Because there is lack of effective soft tissue techniques, osteotomies have become the mainstream surgical approach to compensate for the underlying soft tissue deficiency; osteodesis, a soft tissue nonosteotomy technique, may be a third alternative, but its efficacy is unknown.Questions/purposesWe asked: (1) Can an osteodesis, a distal soft tissue technique, correct hallux valgus satisfactorily in terms of deformity correction and improvement in American Orthopaedic Foot and Ankle Society (AOFAS) score? (2) Is the effectiveness of an osteodesis affected by the patient's age or deformity severity? (3) What complications are associated with this procedure?MethodsBetween February and October 2010, we performed 126 operations to correct hallux valgus, of which 126 (100%) were osteodeses. Sixty-one patients (110 procedures) (87% of the total number of hallux valgus procedures) were available for followup at a minimum of 12 months (mean, 23 months; range, 12-38 months). This group formed our study cohort. During the study period, the general indications for this approach included failed conservative measures for pain relief and metatarsophalangeal angle greater than 20° or intermetatarsal angle greater than 9°. Intermetatarsal cerclage sutures were used to realign the first metatarsal and postoperative fibrosis was induced surgically between the first and second metatarsals to maintain its alignment. The radiologic first intermetatarsal angle, metatarsophalangeal angle, and medial sesamoid position were measured by Hardy and Clapham's methods for deformity and correction evaluation. Clinical results were assessed by the AOFAS score.ResultsThe intermetatarsal angle was improved from a preoperative mean of 14° to 7° (p<0.001; Cohen's d=1.8) at followup, the metatarsophalangeal angle from 31° to 18° (p<0.001; Cohen's d=3.1), the medial sesamoid position from position 6 to 3 (p<0.001; Cohen's d=2.4), and AOFAS hallux score from 68 to 96 points (p<0.001). Neither patient age nor deformity severity affected the effectiveness of the osteodesis in correcting all three radiologic parameters; however, the deformities treated in this series generally were mild to moderate (mean intermetatarsal angle, 14°; range, 9°-22°). There were six stress fractures of the second metatarsal (5%), five temporary metatarsophalangeal joint medial subluxations all resolved in one month by the taping-reduction method without surgery, and six metatarsophalangeal joints with reduced dorsiflexion less than 60°.ConclusionsThe osteodesis is a soft tissue nonosteotomy technique, and provided adequate deformity correction and improvement in AOFAS scores for patients with mild to moderate hallux valgus deformities, although a small number of the patients had postoperative stress fractures of the second ray develop. Future prospective studies should compare this technique with osteotomy techniques in terms of effectiveness of the correction, restoration of hallux function, complications, and long-term recurrence.Level of evidenceLevel IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Project description:BackgroundThe 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.MethodsThis 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.ResultsStrong, 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.ConclusionsStrong 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.

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Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

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Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

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