Modifiable Risk Factors for Prevention in Dupuytren Disease: A UK Biobank Case-Control Study.

BACKGROUND: Dupuytren disease is associated with significant comorbidity and mortality, and it has no existing prevention strategies. It is unclear which modifiable risk factors are most amenable for prevention. This study aimed to determine the strength of modifiable risk factors for Dupuytren disease, and to investigate associations with other diseases. METHODS: Using UK Biobank data, this case-control study analyzed the association between phenotypic variables and Dupuytren disease through multivariable logistic regression. Exposures assessed were age, sex, body mass index, waist-to-hip ratio, Townsend deprivation index, smoking status, alcohol intake, diabetes mellitus, hypertension, cancer, liver disease, respiratory disease, rheumatoid arthritis, epilepsy, psoriasis, and gout. RESULTS: There were 4148 cases and 397,425 controls. Male sex (OR, 3.23; 95% CI, 2.90 to 3.60; P = 1.07 × 10 -100 ), increasing age (OR, 1.08; 95% CI, 1.07 to 1.08; P = 6.78 × 10 -167 ), material deprivation (OR, 1.01; 95% CI, 1.00 to 1.02; P = 0.0305), high-density lipoprotein cholesterol (OR, 1.76; 95% CI, 1.58 to 1.96; P = 3.35 × 10 -24 ), smoking exposure, and alcohol intake were all associated with increased odds of Dupuytren disease. With increasing obesity class, there was approximately 25% decreased odds (OR, 0.774; 95% CI, 0.734 to 0.816; P = 4.71 × 10 -21 ). Diabetes with microvascular or end-organ complications was associated with more than 2.5 times increased odds of Dupuytren disease (OR, 2.59; 95% CI, 1.92 to 3.44; P = 1.92 × 10 -10 ). Within this group, increasing hemoglobin A1c values by 10 mmol/mol, or 0.9%, increased the odds by 31% (OR, 1.31; 95% CI, 1.13 to 1.51; P = 2.19 × 10 -4 ). CONCLUSION: Diabetes and poor glycemic control are major risk factors for Dupuytren disease, which present an opportunity for prevention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Exposure to hand-arm vibrations in the workplace and the occurrence of hand-arm vibration syndrome, Dupuytren's contracture, and hypothenar hammer syndrome: a systematic review and meta-analysis.

This study provides an overview of the relationships between exposure to work-related hand-arm vibration and the occurrence of pre-defined disorders of the hands. We searched Medline, Embase, Web of Science, Cochrane Central, and PsycINFO for cross-sectional and longitudinal studies on the association between work-related vibration exposure and the occurrence of hand-arm vibration syndrome (including vibration-induced white finger), Dupuytren's contracture, or hypothenar hammer syndrome. We used a 16-item checklist for assessing the risk of bias. We present results narratively, and we conducted random effects meta-analyses if possible. We included 10 studies with more than 24,381 participants. Our results showed statistically significant associations between the exposure to hand-arm vibrations and the occurrence of the selected disorders, with pooled odds ratios ranging between 1.35 (95% CI: 1.28 to 2.80) and 3.43 (95% CI: 2.10 to 5.59). Considerable between-study heterogeneity was observed. Our analyses show that exposure to vibrating tools at work is associated with an increased risk for the occurrence of selected disorders of the hands. Due to the majority of studies being cross-sectional, no firm conclusion is possible regarding causal relationships between vibration exposure and disorder occurrence. Future research should specifically address whether reducing exposure to hand-held vibrating tools at work reduces the incidence of the disorders of the hands investigated in this systematic review.

Dupuytren's disease is a work-related disorder: results of a population-based cohort study.

OBJECTIVES: Dupuytren's disease (DD) is a fibroproliferative disorder of the hands, characterised by the development of fibrous nodules and cords that may cause disabling contractures of the fingers. The role of manual work exposure in the aetiology of DD is controversial. We investigated whether current occupational exposure to manual work is associated with DD, and if there is a dose-response relationship. METHODS: In this population-based cohort analysis, we used data from the UK Biobank cohort. Our primary outcome was the presence of DD. The exposure of interest was manual work, measured for each participant in two different ways to allow two independent analyses to be undertaken: (1) the current manual work status of the occupation at the time of recruitment, and (2) a cumulative manual work exposure score, calculated based on the occupational history. We performed propensity score matching and applied a logistic regression model. RESULTS: We included 196 265 participants for the current manual work analysis, and 96 563 participants for the dose-response analysis. Participants whose current occupation usually/always involved manual work were more often affected with DD than participants whose occupation sometimes/never involved manual work (OR 1.29, 95% CI 1.12 to 1.49, p<0.001). There was a positive dose-response relationship between cumulative manual work exposure score and DD. Each increment in cumulative work exposure score increased the odds by 17% (OR 1.17, 95% CI 1.08 to 1.27, p<0.001). CONCLUSIONS: Manual work exposure is a risk factor for DD, with a clear dose-response relationship. Physicians treating patients should recognise DD as a work-related disorder and inform patients accordingly.

Quantitative predictive approaches for Dupuytren disease: a brief review and future perspectives.

In this study we review the current state of the art for Dupuytren's disease (DD), while emphasising the need for a better integration of clinical, experimental and quantitative predictive approaches to understand the evolution of the disease and improve current treatments. We start with a brief review of the biology of this disease and current treatment approaches. Then, since certain aspects in the pathogenesis of this disorder have been compared to various biological aspects of wound healing and malignant processes, next we review some in silico (mathematical modelling and simulations) predictive approaches for complex multi-scale biological interactions occurring in wound healing and cancer. We also review the very few in silico approaches for DD, and emphasise the applicability of these approaches to address more biological questions related to this disease. We conclude by proposing new mathematical modelling and computational approaches for DD, which could be used in the absence of animal models to make qualitative and quantitative predictions about the evolution of this disease that could be further tested in vitro.

Circulating inflammatory cytokines alter transcriptional activity within fibrotic tissue of Dupuytren's disease patients.

Dupuytren's disease is a benign fibroproliferative disorder of the hand that results in disabling digital contractures that impair function and diminish the quality of life. The incidence of this disease has been correlated with chronic inflammatory states, but any direct association between inflammatory cytokines and Dupuytren's disease is not known. We hypothesized that advanced fibroproliferation is associated with increased levels of circulating inflammatory cytokines. Blood and fibrotic cord tissue were collected preoperatively from patients with severe contracture and control patients. Blood plasma concentrations of known inflammatory cytokines were evaluated using a multiplex immunoassay. Proteins from the cord tissue were analyzed by RNA sequencing and immunohistochemistry. Moreover, collagen-rich cords were analyzed using Fourier-transform infrared spectroscopy. The results indicate that patients exhibited significantly elevated circulating inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, and IL-12p70, as compared with controls. Similarly, IL-4 and IL-13 were detected significantly more frequently in Dupuytren's disease as compared with control. RNA sequencing revealed 5311 differentially expressed genes and distinct clustering between diseased and control samples. In addition to increased expression of genes associated with fibroproliferation, we also observed upregulation of transcripts activated by inflammatory cytokines, including prolactin inducible protein and keratin intermediate filaments. IL-2, but not TNF-α, was detected in fibrotic cord tissue by immunohistochemistry. Finally, spectroscopic assays revealed a significant reduction of the collagen content and alterations of collagen cross-linking within the Dupuytren's disease tissues. In total, our results illustrate that patients with severe Dupuytren's disease exhibit substantially elevated circulating inflammatory cytokines that may drive fibroproliferation. Clinical Significance: The results from this study establish the basis for a specific cytokine profile that may be useful for diagnostic testing and therapeutic intervention in Dupuytren's disease.

Factors Associated with the Development, Progression, and Outcome of Dupuytren Disease Treatment: A Systematic Review.

BACKGROUND: The factors typically considered to be associated with Dupuytren disease have been described, such as those in the "Dupuytren diathesis." However, the quality of studies describing them has not been appraised. This systematic review aimed to analyze the evidence for all factors investigated for potential association with the development, progression, outcome of treatment, or recurrence of Dupuytren disease. METHODS: A systematic review of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature databases was conducted using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant methodology up to September of 2019. Articles were screened in duplicate. Prognostic studies were quality assessed using the Quality in Prognosis Study tool. RESULTS: This study identified 2301 records; 51 met full inclusion criteria reporting data related to 54,491 patients with Dupuytren disease. In total, 46 candidate factors associated with the development of Dupuytren disease were identified. There was inconsistent evidence between the association of Dupuytren disease and the presence of "classic" diathesis factors. The quality of included studies varied, and the generalizability of studies was low. There was little evidence describing the factors associated with functional outcome. CONCLUSIONS: This systematic review challenges conventional notions of diathesis factors. Traditional diathesis factors are associated with disease development and recurrence, although they are not significantly associated with poor outcome following intervention based on the current evidence.

Dupuytren's Disease-Etiology and Treatment.

BACKGROUND: The worldwide prevalence of Dupuytren's disease (DD) is 8%. DD is a chronic disease for which there is no cure. Various treatments are available. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed and Embase. RESULTS: Genetic factors account for 80% of the factors involved in causing this disease. Diabetes mellitus, hepatic diseases, epilepsy, and chronic occupational use of vibrating tools are also associated with it. Limited fasciectomy is the most common treatment and is considered the reference standard. Possible complications include persistent numbness in areas where the skin has been elevated, cold sensitivity, and stiffness, with a cumulative risk of 3.6 -39.1% for all complications taken together. The recurrence rate at 5 years is 12-73%. Percutaneous needle fasciotomy is the least invasive method, with more rapid recovery and a lower complication rate than with limited fasciectomy. 85% of patients have a recurrence after an average of 2.3 years. Radiotherapy can be given before contractures arise in patients with high familial risk, or postoperatively in selected patients with a very high individual risk of recurrence. CONCLUSION: Although DD is not curable, good treatments are available. Recurrences reflect the pathophysiology of the disease and should not be considered complications of treatment. When counseling patients about the available treatment options, particularly the modalities and timing of surgery, the physician must take the patient's degree of suffering into account. Nowadays, fast recovery from surgery and less postoperative pain are a priority for many patients. Different surgical methods can be used in combination. It remains difficult to predict the natural course and the time to postoperative recurrence in individual patients; these matters should be addressed in future studies.

Metabolic factors and the risk of Dupuytren's disease: data from 30,000 individuals followed for over 20 years.

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia of the hand. Risk factors include diabetes mellitus (DM), whereas a high body mass index (BMI) is associated with a lower prevalence of DD. The aim of this study was to further elucidate risk and protective factors for the development of DD using longitudinal population-based data from the Malmö Diet and Cancer Study (MDCS). During 1991-1996, the inhabitants aged 46-73 years in the city of Malmö, Sweden were invited to participate in the population-based MDCS (41% participation rate). Data on incident DD were retrieved from Swedish national registers. Associations between DM, alcohol consumption, BMI, and serum apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) at baseline were analysed in multivariable Cox regression models adjusted for known confounders. Among 30,446 recruited participants, 347 men and 194 women were diagnosed with DD during a median follow-up time of 23 years. DM (men HR 2.23; 95% CI 1.50-3.30, women HR 2.69; 95% CI 1.48-4.90) and alcohol consumption (men HR 2.46; 95% CI 1.85-3.27, women HR 3.56; 95% CI 1.95-6.50) were independently associated with incident DD in the Cox regression models. Furthermore, inverse associations with incident DD were found for obesity among men, and ApoB/ApoA1 ratio among both sexes. DM and excess alcohol consumption constituted major risk factors for the development of DD. Furthermore, an inverse association between obesity among men and DD, and also between ApoB/ApoA1 ratio and DD was found in both sexes.

Fibroproliferative disorders and diabetes: Understanding the pathophysiologic relationship between Peyronie's disease, Dupuytren disease and diabetes.

Introduction: Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the tunica albuginea of the penis and fascia of the hand, respectively. Chronic hyperglycaemia due to diabetes mellitus can also lead to tissue injury and fibrosis. A meta-analysis has shown a relationship between Dupuytren disease and diabetes (overall odds ratio, 3.1; 95% confidence interval, 2.7-3.5). This review explores commonalities in the pathogenesis of Peyronie's disease, Dupuytren disease and diabetes. Methods: A search of the PubMed database was conducted using the search terms "diabetes" AND "Peyronie's disease"; and "diabetes" AND "Dupuytren." Results: Genome-wide association and gene expression studies conducted with tissue from people with Peyronie's disease or Dupuytren disease identified signalling pathways associated with wingless-type mammary-tumour virus integration site signalling, extracellular matrix modulation and inflammation. Biochemical studies confirmed the importance of these pathways in the pathogenesis of fibrosis with Peyronie's disease and Dupuytren disease. Dysregulation of matrix metalloproteinase activity associated with extracellular matrix breakdown was implicated in fibroproliferative complications of diabetes and in the aetiology of Peyronie's disease and Dupuytren disease. A notable percentage of people with diabetes have comorbid Peyronie's disease and/or Dupuytren disease. Conclusions: Studies have not been performed to identify fibroproliferative pathways that all 3 conditions might have in common, but data suggest that common pathways are involved in the fibroproliferative processes of Peyronie's disease, Dupuytren disease, and diabetes.

Is Dupuytren's disease an occupational illness?

BACKGROUND: There is growing evidence for the risk of Dupuytren's disease (DD) from occupational exposure. For workers exposed to hand-transmitted vibrations (HTVs) and heavy manual work (HMW) who develop the disease, the inclusion of DD in hand-arm vibration syndrome and diseases of skeletal muscle overload could be beneficial for compensation purposes. AIMS: To assess the risk of DD in workers exposed to HTVs and HMW, and to evaluate the length of exposure times that may significantly affect the development of DD. METHODS: This study included male workers in Kosice, Slovak Republic. Participants were divided into three groups: those exposed to HTVs, those exposed to HMW and controls. We evaluated the association between DD and HTVs, HMW, cardiovascular diseases, metabolic diseases, epilepsy, smoking and alcohol consumption for all groups. We also compared the length of exposure time to HTV and HMW between workers with and without DD. RESULTS: The sample was comprised of 515 men, with 13% suffering from DD. Significant associations were found between DD and HTVs (OR 4.59 [95% CI 2.05-10.32]) and HMV (OR 3.10 [95% CI 1.21-7.91]). Highly significant associations were found between DD and older ages and alcohol consumption as well. No associations were found for the other variables. Exposure times greater than 15 years significantly increased the risk for DD (P < 0.01). CONCLUSIONS: This study confirms a significant association between DD and both HTVs and HMW after long exposures. We suggest that DD should be considered as an occupational disease.

Serious complications and risk of re-operation after Dupuytren's disease surgery: a population-based cohort study of 121,488 patients in England.

Dupuytren's disease (DD) is a common fibro-proliferative disorder of the palm. We estimated the risk of serious local and systemic complications and re-operation after DD surgery. We queried England's Hospital Episode Statistics database and included all adult DD patients who were surgically treated. A longitudinal cohort study and self-controlled case series were conducted. Between 1 April 2007 and 31 March 2017, 121,488 adults underwent 158,119 operations for DD. The cumulative incidence of 90-day serious local complications was low at 1.2% (95% CI 1.1-1.2). However, the amputation rate for re-operation by limited fasciectomy following dermofasciectomy was 8%. 90-day systemic complications were also uncommon at 0.78% (95% CI 0.74-0.83), however operations routinely performed under general or regional anaesthesia carried an increased risk of serious systemic complications such as myocardial infarction. Re-operation was lower than previous reports (33.7% for percutaneous needle fasciotomy, 19.5% for limited fasciectomy, and 18.2% for dermofasciectomy). Overall, DD surgery performed in England was safe; however, re-operation by after dermofasciectomy carries a high risk of amputation. Furthermore, whilst serious systemic complications were unusual, the data suggest that high-risk patients should undergo treatment under local anaesthesia. These data will inform better shared decision-making regarding this common condition.

The worldwide prevalence of the Dupuytren disease: a comprehensive systematic review and meta-analysis.

BACKGROUND: The Dupuytren disease is a benign fibroproliferative disorder that leads to the formation of the collagen knots and fibres in the palmar fascia. The previous studies reveal different levels of Dupuytren's prevalence worldwide; hence, this study uses meta-analysis to approximate the prevalence of Dupuytren globally. METHODS: In this study, systematic review and meta-analysis have been conducted on the previous studies focused on the prevalence of the Dupuytren disease. The search keywords were Prevalence, Prevalent, Epidemiology, Dupuytren Contracture, Dupuytren and Incidence. Subsequently, SID, MagIran, ScienceDirect, Embase, Scopus, PubMed and Web of Science databases and Google Scholar search engine were searched without a lower time limit and until June 2020. In order to analyse reliable studies, the stochastic effects model was used and the I2 index was applied to test the heterogeneity of the selected studies. Data analysis was performed within the Comprehensive Meta-Analysis Software version 2.0. RESULTS: By evaluating 85 studies (10 in Asia, 56 in Europe, 2 in Africa and 17 studies in America) with a total sample size of 6628506 individuals, the prevalence of Dupuytren disease in the world is found as 8.2% (95% CI 5.7-11.7%). The highest prevalence rate is reported in Africa with 17.2% (95% CI 13-22.3%). According to the subgroup analysis, in terms of underlying diseases, the highest prevalence was obtained in patients with type 1 diabetes with 34.1% (95% CI 25-44.6%). The results of meta-regression revealed a decreasing trend in the prevalence of Dupuytren disease by increasing the sample size and the research year (P < 0.05). CONCLUSION: The results of this study show that the prevalence of Dupuytren disease is particularly higher in alcoholic patients with diabetes. Therefore, the officials of the World Health Organization should design measures for the prevention and treatment of this disease.

Nongenetic Factors Associated with Dupuytren's Disease: A Systematic Review.

BACKGROUND: Dupuytren's disease is a common complex disease caused by genetic and nongenetic factors. The role of many nongenetic risk factors is still unclear and debatable. This study aimed to systematically review the association between Dupuytren's disease and nongenetic risk factors. METHODS: A search strategy was developed based on the Population, Exposure, Comparison, Outcomes and Study framework. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted in MEDLINE, Embase, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to November of 2018. Title and abstract and then full-text screening against eligibility criteria was performed independently by two reviewers, and consensus was achieved by a third reviewer. The Effective Public Health Practice Project and the Oxford Centre for Evidence Based Medicine tools were used to assess study quality and to evaluate the level of evidence of included studies, respectively. RESULTS: Reviewers identified 4434 studies, of which 54 were included in the analysis. There was strong evidence for the association between Dupuytren's disease and advanced age, male sex, family history of Dupuytren's disease, and diabetes mellitus. Furthermore, heavy alcohol drinking, cigarette smoking, and manual work exposure showed a significant dose-response relationship. The quality of the included studies was mainly low or moderate, and most studies were level 3 or 4 on the Oxford Centre for Evidence Based Medicine scale. CONCLUSIONS: The study results show a strong association between Dupuytren's disease and advanced age, male sex, family history of Dupuytren's disease, diabetes mellitus, heavy alcohol drinking, cigarette smoking, and manual work exposure. Further studies are required to explain the causal relationship of these associations.

Dupuytren's Contracture: Incidence of Injury-Induced Cases and Specific Clinical Expression.

Background and objectives: Dupuytren's contracture is a chronic fibroproliferative hand disorder with a varying pattern of genetic predisposition across different regions and populations. Traumatic events have been found to have influence on the development of this illness and are likely to trigger different clinical forms of this disease. The aim of this study was to evaluate the phenomenon of development of Dupuytren's contracture (DC) following an acute injury to the hand, and to observe the incidence and clinical diversity of such cases in daily clinical practice. Materials and Methods: We collected data of patients presenting with primary Dupuytren's contracture in the Lithuanian population and evaluated the occurrence and clinical manifestation of this specific type of DC, arising following acute hand trauma. The diagnosis of DC was based on clinical signs and physical examination. Digit contractures were measured by goniometry, and the staging was done according to Tubiana classification. Injury-induced (injury-related) cases were identified using the "Criteria for recognition of Dupuytren's contracture after acute injury" (established by Elliot and Ragoowansi). Results: 29 (22%) of a total of 132 cases were injury-induced DCs. Twenty-six of 29 patients in this group presented with stage I-II contractures. Duration of symptoms was 6 (SD 2.2) and 3.8 (SD 2.2) years in the injury-related and injury-unrelated DC groups, respectively. Mean age on the onset of symptoms in the injury-induced and non-injury-induced groups was 52 (SD 10.7) and 56 (SD 10.9), respectively. Patients from both groups expressed strong predisposition towards development of DC. Conclusions: Around one-fifth of patients seeking treatment for primary Dupuytren's contracture seemed to suffer from injury-induced Dupuytren's contracture. We noted that injury to the wrist and hand seems to trigger the development of less progressive Dupuytren's contracture in younger age. Prospective randomized studies are required to confirm our findings.

Dupuytren's Disease and exposure to vibration: Systematic review and Meta-analysis.

INTRODUCTION: Dupuytren's Disease (DD) occurs frequently in the entire population. Several risk factors are well known, including diabetes, alcohol, and age. In this meta-analysis, we assessed the role of occupational vibration exposure in the risk of DD, an issue currently under debate. METHODS: We searched PubMed, Google Scholar, and the Cochrane Library to find references up to June 2019. DD prevalence was calculated using meta-proportion analysis. Differences in characteristics between DD patients and controls were expressed as standardized mean differences using the inverse of variance method or percentages using also meta-proportion analysis. We performed meta-regression analyses to assess the effects of alcohol, smoking, age, and sex on the DD incidence for the patients with DD that were exposed to vibrations. RESULTS: We included 9 studies, comprising a total of 60,570 patients, including 1,804 DD patients. Prevalence of DD was 9.8% (95%CI: 5.9-14.4%). Compared with controls, patients with DD were older, more diabetic, more smokers and with a higher consumption of alcohol. Meta-analysis of the nine longitudinal studies comparing DD occurrence between patients exposed to vibration (626 of 6825) or not (1220 of 52,502) revealed a significantly increased DD incidence among patients with vibration exposure compared with controls (OR=2.87; 95%CI: 1.41-5.84). In metaregression we found no significant influence of all parameters on DD. CONCLUSION: Age and environmental factors had no effect on DD prevalence among patients exposed to vibrations, despite a 10% prevalence in this group. Using vibration tools at work should be recognized as an important risk factor of developing DD.

Association between occupational exposure and Dupuytren's contracture using a job-exposure matrix and self-reported exposure in the CONSTANCES cohort.

BACKGROUND: Although several studies highlighted an association between occupational exposure and Dupuytren's contracture (DC), they were often limited by the highly selected population. We aimed to study this association using a job-exposure matrix (JEM) and self-reported exposure in a large cohort. METHODS: From CONSTANCES, a French population-based prospective cohort, we retrieved sex, age, social position, alcohol/tobacco intake and diabetes. Lifetime exposures were assessed by two different methods: with the biomechanical JEM 'JEM Constances', we assessed exposure to vibration and/or forearm rotation for participants whose work history was available, and from a self-administered questionnaire, we retrieved self-reported exposure to arduous work and/or carrying heavy loads. Surgery for DC was collected from the French Health Administrative database from 2009 to 2016. Multivariate logistic regression models adjusted for confounders were built to assess association between surgery for DC and occupational exposures. RESULTS: Work history was retrieved for 23 795 subjects among whom 98 underwent surgery for DC. Adjusted OR (aOR) was 2.08 (1.03-4.2) for being ever exposed to vibration and/or forearm rotation for subjects <60 years and 1.20 (0.69-2.08) for subjects ≥60 years. Data for self-reported exposure were available for 81 801 participants among whom 367 underwent surgery for DC. aOR for being exposed more than 20 years to arduous work and/or carrying heavy loads was 2.01 (1.32-3.04) for subjects <60 years and 1.04 (0.7-1.54) for subjects ≥60. CONCLUSIONS: Manual work is associated with surgery for DC among younger subjects. Monitoring exposed workers is important to prevent future functional limitations.

Integrative analysis of Dupuytren's disease identifies novel risk locus and reveals a shared genetic etiology with BMI.

Dupuytren's disease is a common inherited tissue-specific fibrotic disorder, characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia of the hand. Although genome-wide association study (GWAS) have identified 24 genomic regions associated with Dupuytrens risk, the biological mechanisms driving signal at these regions remain elusive. We identify potential biological mechanisms for Dupuytren's disease by integrating the most recent, largest GWAS (3,871 cases and 4,686 controls) with eQTLs (47 tissue panels from five consortia, total n = 3,975) to perform a transcriptome-wide association study. We identify 43 tissue-specific gene associations with Dupuytren's risk, including one in a novel risk region. We also estimate the genome-wide genetic correlation between Dupuytren's disease and 45 complex traits and find significant genetic correlations between Dupuytren's disease and body mass index (BMI), type II diabetes, triglycerides, and high-density lipoprotein (HDL), suggesting a shared genetic etiology between these traits. We further examine local genetic correlation to identify 8 and 3 novel regions significantly correlated with BMI and HDL respectively. Our results are consistent with previous epidemiological findings showing that lower BMI increases risk for Dupuytren's disease. These 12 novel risk regions provide new insight into the biological mechanisms of Dupuytren's disease and serve as a starting point for functional validation.

Risk Factors, Disease Associations, and Dupuytren Diathesis.

Dupuytren disease (DD) is a benign, fibroproliferative disease of unknown cause. The disease predominantly affects the palms of the hands, causing permanent digital contracture of affected digits. DD is a late-onset disease and is often progressive, irreversible, and bilateral. The disease has a significant impact on the health care economy. The mainstay of treatment of DD is surgical excision of diseased palmar fascia. There is evidence of genetic susceptibility. This article introduces the epidemiology of DD and examines the Dupuytren diathesis to highlight the importance of identifying clinical severity in relation to patient counseling and recurrence risk following treatment.