Paternal environment effects are driven by female reproductive fluid but not sperm age in an external fertilizer.

Sperm ageing after ejaculation can generate paternal environment effects that impact offspring fitness. In many species, female reproductive fluids (FRFs), i.e. ancillary fluids released by eggs or within the female reproductive tract, may protect sperm from ageing and can additionally interact with sperm to influence offspring viability. This raises the intriguing prospect that FRFs may alleviate paternal effects associated with sperm ageing. Here, we test this novel hypothesis using the broadcast spawning mussel, Mytilus galloprovincialis. We show that incubating sperm in FRF prior to fertilization increases offspring viability, and that these effects occur independently of sperm age. Our results provide novel evidence that FRFs allow females to selectively bias fertilization toward higher quality sperm within an ejaculate, which in turn yields more viable offspring. We consider this FRF-mediated paternal effect in the context of female physiological control over fertilization and the transgenerational effects of female-regulated haploid selection.

Testing for age-dependent effects of dietary restriction on the strength of condition dependence in ejaculate traits in the guppy (Poecilia reticulata).

Ejaculates can be costly to produce and depend on an individual's condition, defined as the pool of resources allocated to fitness. A method for assessing condition dependence is to manipulate resource availability and test for a reduction in trait expression. Here, we assess the effects of dietary restriction on two determinants of reproductive fitness in the guppy Poecilia reticulata-sperm production and sperm motility. Importantly, we administered dietary restriction at distinct developmental stages to test: (1) whether dietary restriction, when applied exclusively to juveniles, compromised the ejaculates of newly mature males; (2) whether any observed effects of dietary restriction seen in (1) were reversible when fish returned to an unrestricted diet; and (3) whether dietary restriction applied exclusively to adults influenced ejaculates. We found detrimental effects of resource limitation on both traits, and these were consistent across the three developmental stages tested. Furthermore, dietary restriction reduced male body weight, but this was partially reversed when diet-stressed juveniles (i.e. group 2) returned to unrestricted diets. This latter result suggests that diet-stressed males may sacrifice growth in order to maintain their investment in ejaculates. Together these findings underscore the importance of resource acquisition in determining the expression of ejaculate traits.

Female reproductive fluids 'rescue' sperm from phenotypic ageing in an external fertilizer.

Female reproductive fluids (FRFs) serve key reproductive functions in sexually reproducing animals, including modifying the way sperm swim and detect eggs, and influencing sperm lifespan. Despite the central role of FRF during fertilization, we know surprisingly little about sperm-FRF interactions under different environmental conditions. Theory suggests that in external fertilizers FRF may 'rescue' sperm from ageing effects as they search to fertilize eggs. Here, we test the interaction between these two fundamental properties of the fertilization environment, ejaculate age (i.e. time since ejaculation) and FRF, on a range of functional sperm phenotypes in a broadcast spawning mussel, Mytilus galloprovincialis. We found that the effects of ejaculate age on multivariate sperm motility traits and total sperm motility were altered by FRF, and that longer-lived sperm exhibit stronger, likely more advantageous, responses to FRF after periods of ageing. We also detected significant among-male variation in the relationship between sperm motility traits and ejaculate age; notably, these patterns were only revealed when sperm encountered FRF. Collectively these findings underscore the importance of considering female reproductive physiology when interpreting ageing-related declines in sperm motility, as doing so may expose importance sources of variation in sperm phenotypic plasticity among males and environments.

The Amelioration of Grazing through Physiological Integration by a Clonal Dune Plant.

Rhizomatous growth and associated physiological integration can allow a clonal dune species to potentially compensate for the selective removal of leaves associated with herbivory. Hydrocotyle bonariensis is a rhizomatous clonal plant species that is abundant in the coastal dune environments of the southeastern United States that are inhabited by large feral horse populations. H. bonariensis has been shown to integrate resources among ramets within extensive clones as an adaptation to resource heterogeneity in sandy soils. In this study, we hypothesized that clonal integration is a mechanism that promotes H. bonariensis persistence in these communities, despite high levels of herbivory by feral horses. In a field experiment, we used exclosures to test for herbivory in H. bonariensis over a four-month period. We found that feral horses utilized H. bonariensis as a food species, and that while grazing will suppress clonal biomass, H. bonariensis is able to maintain populations in a high grazing regime with and without competition present. We then conducted an experiment in which portions of H. bonariensis clones were clipped to simulate different levels of grazing. Half of the clones were severed to eliminate the possibility of integration. We found that after 12 weeks, the mean number of leaves and ramets increased as the grazing level increased, for integrated clones. Integrated clones had significantly increased biomass production compared to the severed equivalents. Our research suggests that rhizomatous growth and physiological integration are traits that allow clonal plant species to maintain populations and to tolerate grazing in coastal dune environments.

The use of microfluidic devices in studies of differential sperm chemotaxis.

Differential sperm chemotaxis describes differences among male-female pairings in chemotactic responses of sperm to egg (or female)-derived chemical attractants. Microfluidic devices provide powerful platforms in which to study this complex gamete interaction. Here, we describe key challenges and potential solutions in applying this state-of-the-art technique to differential sperm chemotaxis.

Personality, sperm traits and a test for their combined dependence on male condition in guppies.

There is evidence that animal personality can affect sexual selection, with studies reporting that male behavioural types are associated with success during pre- and post-copulatory sexual selection. Given these links between personality and sexual traits, and the accumulating evidence that their expression can depend on an individual's dietary status (i.e. condition), a novel prediction is that changes in a male's diet should alter both the average expression of personality and sexual traits, and their covariance. We tested these predictions using the guppy Poecilia reticulata, a species previously shown to exhibit strong condition dependence in ejaculate traits and a positive correlation between sperm production and individual variation in boldness. Contrary to expectation, we found that dietary restriction-when administered in mature adult males-did not affect the expression of either behavioural (boldness and activity) or ejaculate traits, although we did find that males subjected to dietary stress exhibited a positive association between sperm velocity and boldness that was not apparent in the unrestricted diet group. This latter finding points to possible context-dependent patterns of covariance between sexually selected traits and personalities, which may have implications for patterns of selection and evolutionary processes under fluctuating environmental conditions.

How long does an elbow replacement last? A systematic review and meta-analysis of case-series and national registry reports with more than 10 years of follow-up.

BACKGROUND AND PURPOSE: This study aims to determine, for the first time, generalizable data on the longevity and long-term function of elbow replacements. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles reporting 10-year or greater survival of total elbow replacements (TERs) and distal humeral hemiarthroplasty. Implant survival and patient reported outcome measures (PROMs) data were extracted. National joint replacement registries were also analyzed. We weighted each series and calculated a pooled survival estimate at 10, 15, and 20 years. For PROMs we pooled the standardized mean difference (SMD) at 10 years. FINDINGS: Despite its widespread use, we identified only 9 series reporting all-cause survival of 628 linked TERs and 610 unlinked TERs and no series for distal humeral hemiarthroplasty. The studied population was treated for rheumatoid arthritis in over 90% of cases. The estimated 10-year survival for linked TERs was 92% (95% CI 90-95) and unlinked TERs 84% (CI 81-88). 2 independent registries contributed 32 linked TERs and 530 unlinked TERs. The pooled registry 10-year survival for unlinked TERs was 86% (CI 83-89). Pooled 10-year PROMs from 164 TERs (33 linked and 131 unlinked), revealed a substantial improvement from baseline scores (SMD 2.7 [CI 1.6-3.8]). INTERPRETATION: Over 80% of all elbow replacements and over 90% of linked elbow replacements can last more than 10 years with sustained patient-reported benefits. This information is long overdue and will be particularly useful to patients as well as healthcare providers.

Hemiarthroplasty or total elbow arthroplasty for unreconstructable distal humeral fractures in patients aged over 65 years : a systematic review and meta-analysis of patient outcomes and complications.

AIMS: Arthroplasty is being increasingly used for the management of distal humeral fractures (DHFs) in elderly patients. Arthroplasty options include total elbow arthroplasty (TEA) and hemiarthroplasty (HA); both have unique complications and there is not yet a consensus on which implant is superior. This systematic review asked: in patients aged over 65 years with unreconstructable DHFs, what differences are there in outcomes, as measured by patient-reported outcome measures (PROMs), range of motion (ROM), and complications, between distal humeral HA and TEA? METHODS: A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on PROMs, ROM, and complications. PROMs and ROM results were reported descriptively and a meta-analysis of complications was conducted. Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROSPERO (CRD42021228329). RESULTS: A total of 29 studies met the inclusion and exclusion criteria. The mean Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) score was 19.6 (SD 7.5) for HA and 38 (SD 11.9) for TEA and the mean abbreviated version of DASH was 17.2 (SD 13.2) for HA and 24.9 (SD 4.8) for TEA. The Mayo Elbow Performance Score was the most commonly reported PROM across included studies, with a mean of 87 (SD 5.3) in HA and 88.3 (SD 5) in TEA. High complication rates were seen in both HA (22% (95% confidence interval (CI) 5 to 44)) and TEA (21% (95% CI 13 to 30), but no statistically significant difference identified. CONCLUSION: This systematic review has indicated PROMs and ROM mostly favouring HA, but with a similarly high complication rate in the two procedures. However, due to the small sample size and heterogeneity between studies, strength of evidence for these findings is low. We propose further research in the form of a national randomized controlled trial. Cite this article: Bone Joint J 2022;104-B(5):559-566.

Ocean acidification alters sperm responses to egg-derived chemicals in a broadcast spawning mussel.

The continued emissions of anthropogenic carbon dioxide are causing progressive ocean acidification (OA). While deleterious effects of OA on biological systems are well documented in the growth of calcifying organisms, lesser studied impacts of OA include potential effects on gamete interactions that determine fertilization, which are likely to influence the many marine species that spawn gametes externally. Here, we explore the effects of OA on the signalling mechanisms that enable sperm to track egg-derived chemicals (sperm chemotaxis). We focus on the mussel Mytilus galloprovincialis, where sperm chemotaxis enables eggs to bias fertilization in favour of genetically compatible males. Using an experimental design based on the North Carolina II factorial breeding design, we test whether the experimental manipulation of seawater pH (comparing ambient conditions to predicted end-of-century scenarios) alters patterns of differential sperm chemotaxis. While we find no evidence that male-female gametic compatibility is impacted by OA, we do find that individual males exhibit consistent variation in how their sperm perform in lowered pH levels. This finding of individual variability in the capacity of ejaculates to respond to chemoattractants under acidified conditions suggests that climate change will exert considerable pressure on male genotypes that can withstand an increasingly hostile fertilization environment.

Ecology of fear in highly invasive fish revealed by robots.

Invasive species threaten biodiversity and ecosystem functioning. We develop an innovative experimental approach, integrating biologically inspired robotics, time-series analysis, and computer vision, to build a detailed profile of the effects of non-lethal stress on the ecology and evolution of mosquitofish (Gambusia holbrooki)-a global pest. We reveal that brief exposures to a robotic predator alter mosquitofish behavior, increasing fear and stress responses, and mitigate the impact of mosquitofish on native tadpoles (Litoria moorei) in a cause-and-effect fashion. Effects of predation risk from the robot carry over to routine activity and feeding rate of mosquitofish weeks after exposure, resulting in weight loss, variation in body shape, and reduction in the fertility of both sexes-impairing survival, reproduction, and ecological success. We capitalize on evolved responses of mosquitofish to reduce predation risk-neglected in biological control practices-and provide scientific foundations for widespread use of state-of-the-art robotics in ecology and evolution research.

Development of a core outcome set for lateral elbow tendinopathy (COS-LET) using best available evidence and an international consensus process.

OBJECTIVES: To develop a core outcome set for lateral elbow tendinopathy (COS-LET) and to provide guidance for outcome evaluation in future studies. METHODS: We implemented a multi-stage mixed-methods design combining two systematic reviews, domain mapping of outcome measurement instruments to the core domains of tendinopathy, psychometric analysis of instruments, two patient focus groups and a Delphi study incorporating two surveys and an international consensus meeting. Following the OMERACT guidelines, we used a 70% threshold for consensus. RESULTS: 38 clinicians/researchers and 9 patients participated. 60 instruments were assessed for inclusion. The only instrument that was recommended for the COS-LET was Patient Rated Tennis Elbow Evaluation (PRTEE) for the disability domain. Interim recommendations were made to use: the PRTEE function subscale for the function domain; PRTEE pain subscale items 1, 4 and 5 for the pain over a specified time domain; pain-free grip strength for the physical function capacity domain; a Numerical Rating Scale measuring pain on gripping for the pain on activity/loading domain; and time off work for the participation in life activities domain. No recommendations could be made for the quality-of-life, patient rating of condition and psychological factors domains. CONCLUSIONS: The COS-LET comprises the PRTEE for the disability domain. Interim-use recommendations included PRTEE subscales, time off work, pain-free grip strength and a Numerical Rating Scale measuring pain on gripping. Further work is required to validate these interim measures and develop suitable measures to capture the other domains.

Density-dependent patterns of multivariate selection on sperm motility and morphology in a broadcast spawning mussel.

Sperm cells exhibit extraordinary phenotypic variation, both among taxa and within individual species, yet our understanding of the adaptive value of sperm trait variation across multiple contexts is incomplete. For species without the opportunity to choose mating partners, such as sessile broadcast spawning invertebrates, fertilization depends on gamete interactions, which in turn can be strongly influenced by local environmental conditions that alter the concentration of sperm and eggs. However, the way in which such environmental factors impact phenotypic selection on functional gamete traits remains unclear in most systems. Here, we analyze patterns of linear and nonlinear multivariate selection under experimentally altered local sperm densities (densities within the capture zone of eggs) on a range of functionally important sperm traits in the broadcast spawning marine mussel, Mytilus galloprovincialis. Specifically, we assay components of sperm motility and morphology across two fertilization environments that simulate either sperm limitation (when there are too few sperm to fertilize all available eggs), or sperm saturation (when there are many more sperm than required for fertilization, and the risk of polyspermy and embryonic failure is heightened). Our findings reveal that the strength, form, and targets of selection on sperm depend on the prevailing fertilization environment. In particular, our analyses revealed multiple significant axes of nonlinear selection on sperm motility traits under sperm limitation, but only significant negative directional selection on flagellum length under sperm saturation. These findings highlight the importance of local sperm densities in driving the adaptation of sperm phenotypes, particularly those related to sperm motility, in broadcast spawning invertebrates.

What is the patient experience following revision knee replacement: A systematic review and meta-analysis of the medium term patient reported outcomes.

AIMS: Revision knee replacement is an increasingly common procedure, however, information on patient-focused outcomes is limited. This systematic review and meta-analysis aimed to investigate the medium-term patient reported outcomes following a revision knee replacement. METHODS: We performed a systematic review of MEDLINE and EMBASE (from inception to 1st March 2021) for articles reporting five year or greater patient reported outcome measures (PROMs) following revision knee replacement. A meta-analysis of PROMs data was undertaken using the Standardised Mean Difference (SMD). Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROPSERO (CRD42021199289). RESULTS: A total of 23 studies met the inclusion criteria containing 2414 patients at a mean minimum follow-up of 74 months (60-122). The reporting of PROMs were poorly standardised with several PROMs being used. The most commonly reported patient reported outcome was the Knee Society Score reported in 65% of studies (15/23). A meta-analysis of 629 eligible patients undergoing revision knee replacement revealed a significant improvement in pre-operative state with a SMD 2·05 95% CI 0.87, 3.23. CONCLUSION: This systematic review has found a significant and sustained improvement in patient-reported outcomes following a revision knee arthroplasty beyond five years. We found a variation in the usage and administration of PROMs which hinders a clear synthesis of results. Furthermore, the PROMs have not been robustly tested for validity in the context of a revision knee replacement.

Mid-term results of Eclipse total shoulder arthroplasty.

AIMS: The use and variety of stemless humeral components in anatomical total shoulder arthroplasty (TSA) have proliferated since their advent in 2004. Early outcomes are reassuring but independent mid-term results are scarce. This independent study reports a consecutive series of 143 Eclipse stemless shoulder prostheses with a minimum five-year (5 to 10) follow-up. METHODS: Outcomes of 143 procedures undertaken for all indications in 131 patients were reviewed, with subset analysis of those for osteoarthritis (OA) (n = 99). The primary outcome was the Oxford Shoulder Score (OSS) at a minimum of five years. Secondary outcomes were ranges of motion and radiological analysis of humeral radiolucency, rotator cuff failure, and glenoid loosening. RESULTS: Mean OSS at mean follow-up of 6.67 years (5.0 to 10.74) was 40.12 (9 to 48), with no statistically significant difference between those implanted for a non-OA indication and those for OA (p = 0.056) or time-dependent deterioration between two years and five years (p = 0.206). Ranges of motion significantly improved compared with preoperative findings and were maintained between two and five years with a mean external rotation of 38° (SD 18.1, 0 to 100) and forward elevation of 152° (SD 29.9, 90 to 180). Of those components with radiographs suitable for analysis (n = 83), 23 (28%) were found to have a least one humeral radiolucent line, which were predominantly incomplete, less than 2 mm, and in a single anatomical zone. No humeral components were loose. A radiolucent line was present around 22 (15%) of glenoid components, and 15 (10%) of components had failed. Rotator cuff failure was found in 21 (15%) components. The mean time to either glenoid or rotator cuff failure was greater than three years following implantation. Survivorship was 96.4% (95% CI 91.6 to 98.5, number at risk 128) at five years, and 94.3% (95% CI 88.2 to 97.3, number at risk 76) at seven years, both of which compare favourably with best results taken from available registries. CONCLUSION: Functional and radiological outcomes of the Eclipse stemless TSA are excellent, with no loose humeral components at minimum five-year follow-up. The presence of radiolucent lines is of interest and requires long-term observation but does not impact on the clinical results. Of the eight revisions required, this was predominantly for glenoid and rotator cuff failure. Cite this article: Bone Joint J 2022;104-B(1):83-90.

Even experts cannot agree on the optimal use of platelet-rich plasma in lateral elbow tendinopathy: an international Delphi study.

BACKGROUND: Platelet-rich plasma (PRP) is widely used in the management of lateral elbow tendinopathy (LET) despite conflicting evidence on its effectiveness. With high levels of user experience, this study aimed to assess consensus amongst experts on its clinical use. METHODS: A three-round international Delphi study was conducted. Participants were invited through national society mailing lists and contact lists derived from a systematic search of the literature on PRP. In round one, a primary working group developed 40 statements on PRP preparation and clinical application. In rounds two and three, an international group of researchers on PRP and clinical users of the device scored their levels of agreement with the statements on a five-point scale. Consensus was defined as an interquartile range of ≤ 1. RESULTS: Consensus of agreement was only reached for 17/40 (42.5%) statements. For statements on PRP formulation, consensus of agreement was reached in 2/6 statements (33%). Only limited consensus on the contraindications, delivery strategy and delivery technique was achieved. CONCLUSION: Experts reached very limited consensus on the use of PRP in LET. High levels of user experience have not resulted in a convergence of opinion on the technical components of PRP formulation and delivery, substantiating the need for further studies and improved trial reporting.

Fitness consequences of targeted gene flow to counter impacts of drying climates on terrestrial-breeding frogs.

Targeted gene flow (TGF) could bolster the adaptive potential of isolated populations threatened by climate change, but could also lead to outbreeding depression. Here, we explore these possibilities by creating mixed- and within-population crosses in a terrestrial-breeding frog species threatened by a drying climate. We reared embryos of the crawling frog (Pseudophryne guentheri) on wet and dry soils and quantified fitness-related traits upon hatching. TGF produced mixed outcomes in hybrids, which depended on crossing direction (origin of gametes from each sex). North-south crosses led to low embryonic survival if eggs were of a southern origin, and high malformation rates when eggs were from a northern population. Conversely, east-west crosses led to one instance of hybrid vigour, evident by increased fitness and desiccation tolerance of hybrid offspring relative to offspring produced from within-population crosses. These contrasting results highlight the need to experimentally evaluate the outcomes of TGF for focal species across generations prior to implementing management actions.

A systematic review of the complications of contemporary total elbow arthroplasty.

BACKGROUND: Total elbow arthroplasty is a low volume procedure. We aimed to evaluate complication rates and cumulative percentages associated with the most frequently used contemporary implants and for the commonest indications. METHODS: A systematic literature search of all studies reporting complications following total elbow arthroplasty with 12-month minimum follow-up was undertaken. Quality of studies was assessed with the Methodological-Index-for-Non-Randomised-studies criteria. British NJR data identified the most common UK prostheses and indications. The complication rates for all undesirable events contributing to patient outcome were extracted and cumulative percentages were calculated. RESULTS: One hundred seventeen studies were screened, 12 studies included, totalling 815 procedures. Mean follow-up was 3.8 years. The overall complication cumulative percentage was 60.7%, significantly higher than that seen in other joint arthroplasty, including a 6.5% deep infection rate. Nerve injury was comparable between implants at around 4.1%. Radiographic loosening had a cumulative rate of 17.2%. Revision for symptomatic aseptic loosening was 6.3%. CONCLUSIONS: This is the largest systematic review of the complications of total elbow arthroplasty. Surgeons should be aware of differing complications related to their implant of choice, each having its own specific complication. Trauma as an indication appears to have an increased complication rates compared to inflammatory arthropathy. There is a lack of literature regarding the independent results of osteoarthritis as a specific indication for total elbow arthroplasty.

Prosthetic joint infection of the knee - arthroscopic biopsy identifies more and different organisms than aspiration alone.

BACKGROUND: Prosthetic joint infection (PJI) causes significant morbidity and mortality following knee replacement surgery. Identifying causative organisms and antibiotic sensitivities is critical in increasing the chance of infection eradication. This study investigated whether biopsy alone was superior to aspiration alone for serological diagnosis in PJI following knee replacement. Secondly, we investigated whether biopsy identifies the same or new/different microbiological flora as aspiration. METHODS: Since December 2014, the Exeter Knee Reconstruction Unit (EKRU) has prospectively collated data regarding all PJIs referred from our local/regional network which have been reviewed via our Multi-Disciplinary Team (MDT). We identified and included consecutive patients from this MDT from Dec.2014-Mar.2020 and analysed their electronic records. Statistical analysis was performed using Stata. RESULTS: 65/100 patients studied had both pre-operative aspiration and biopsy. 31/65 (48%) had positive aspiration and biopsies. No aspirate samples were positive with corresponding biopsies negative. In 19/65 (29%) of infection positive patients, biopsy identified new (7) or additional (12) organisms not identified by aspiration. Aspiration had a sensitivity of 70%, specificity of 88%, positive predictive value of 90.3% and negative predictive value of 64.7%. Biopsy had a sensitivity of 97.5%, specificity of 88%, positive predictive value of 92.9% and negative predictive value of 95.7%. CONCLUSION: In 29% of confirmed PJI cases, arthroscopic biopsy identified either additional organisms in a polymicrobial PJI when compared to aspiration, or new positive results when aspiration alone was negative. This study demonstrates the benefits of arthroscopic biopsy for serological diagnosis in cases of knee PJI and aids treatment planning.

The thermal environment of sperm affects offspring success: a test of the anticipatory paternal effects hypothesis in the blue mussel.

There has been an explosion of recent evidence that environments experienced by fathers or their ejaculates can influence offspring phenotypes (paternal effects). However, little is known about whether such effects are adaptive, which would have far-reaching implications for the many species facing rapidly changing environments. For example, some arguments suggest paternal effects might be a source of cross-generational plasticity, preparing offspring to face similar conditions to their father (anticipatory hypothesis). Alternatively, ejaculate-mediated effects on offspring may be non-adaptive by-products of stress. Here, we conduct an experiment to distinguish between these predictions, exposing ejaculates of the externally fertilizing mussel Mytilus galloprovincialis to ambient (19°C) and high (24°C) temperatures, then rearing offspring groups in temperatures that match and mismatch those of sperm. We find that, overall, high temperature-treated sperm induced higher rates of normal offspring development and higher success in transitioning to second-stage larvae, which may represent adaptive epigenetic changes or selection on sperm haplotypes. However, the progeny of high temperature-treated sperm did not perform better than those of ambient temperature-treated sperm when rearing temperatures were high. Overall, these findings offer little support for the anticipatory hypothesis and suggest instead that beneficial paternal effects may be eroded when offspring develop under stressful conditions.

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.