The perspective of current and retired world class, elite and national athletes on the inclusion and eligibility of transgender athletes in elite sport.

There has been limited empirical study allowing athletes to voice their opinions on transgender participation in elite sport. This study surveyed 175 national, elite and world class athletes eligible to compete in the female category regarding transgender inclusion and eligibility. The study compared current Olympic versus current Olympic Recognised sports, elite versus world class, and current versus retired Olympic sport athletes. Most athletes favoured biological sex categorisation (58%) and considered it unfair for trans women to compete in the female category, except for precision sports. This view was held most strongly by world class athletes regarding their own sport (77% unfair, 15% fair). For trans men inclusion in the male category, most athletes considered it fair, except for Olympic sport athletes regarding contact sports (49% unfair, 27% fair) and sports heavily reliant on physical capacity (53% unfair, 29% fair). Notwithstanding those views, athletes (81%) believed sporting bodies should improve inclusivity for transgender athletes. Opinion varied somewhat according to career stage, competitive level and sport type. Nevertheless, athletes in the present study favoured categorisation by biological sex and did not support trans women eligibility for the female category in sports reliant on performance-related biological factors that differ between sexes.

Sensitivity of Parity-Violating Electron Scattering to a Dark Photon.

We explore the sensitivity of the parity-violating electron scattering (PVES) asymmetry in both elastic and deep-inelastic scattering to the properties of a dark photon. Given advances in experimental capabilities in recent years, there are interesting regions of parameter space where PVES offers the chance to discover new physics in the near future. There are also cases where the existence of a dark photon could significantly alter our understanding of the structure of atomic nuclei and neutron stars as well as parton distribution functions.

Seasonality of Radon-222 near the surface at King Sejong Station (62°S), Antarctic Peninsula, and the role of atmospheric circulation based on observations and CAM-Chem model.

We examined the seasonal cycle of radon concentration observed at King Sejong Station (KSG, 62°S), Antarctic Peninsula, during the period 2013-2016. The distribution of monthly radon concentration was found to be highly positively skewed from March through October (austral autumn to spring) due to large numbers of short-lived periods of high radon concentration. The global atmospheric chemistry model (CAM-Chem), which includes all global terrestrial sources of radon except for those in Antarctica, well reproduces the observed seasonal cycle of monthly-mean radon concentration at KSG. Further offline experiments suggest that uncertainties in radon emissions over South America and the Southern Ocean should be improved for the simulations of radon in Antarctica. The results demonstrate that seasonally varying transport of radon in the boundary layer from South America substantially affects the seasonality of monthly mean radon concentration at KSG. The composite analyses further reveal that high radon events at KSG are the result of a distinct east-west dipole-like structure associated with surface cyclonic circulation over the Bellingshausen Sea and anticyclonic circulation in the Weddell Sea. This atmospheric pattern provides favorable conditions for radon transport into KSG from the northwest. The relationship between radon concentration at KSG and climate variability is also discussed in this study.

Bone mineral density in high-level endurance runners: Part B-genotype-dependent characteristics.

PURPOSE: Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. METHOD: Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. RESULTS: Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC + CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG + GG genotype runners also had 5% higher leg BMD than AG + GG genotype non-athletes. CONCLUSION: We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others.

Bone mineral density in high-level endurance runners: part A-site-specific characteristics.

PURPOSE: Physical activity, particularly mechanical loading that results in high-peak force and is multi-directional in nature, increases bone mineral density (BMD). In athletes such as endurance runners, this association is more complex due to other factors such as low energy availability and menstrual dysfunction. Moreover, many studies of athletes have used small sample sizes and/or athletes of varying abilities, making it difficult to compare BMD phenotypes between studies. METHOD: The primary aim of this study was to compare dual-energy X-ray absorptiometry (DXA) derived bone phenotypes of high-level endurance runners (58 women and 45 men) to non-athletes (60 women and 52 men). Our secondary aim was to examine the influence of menstrual irregularities and sporting activity completed during childhood on these bone phenotypes. RESULTS: Female runners had higher leg (4%) but not total body or lumbar spine BMD than female non-athletes. Male runners had lower lumbar spine (9%) but similar total and leg BMD compared to male non-athletes, suggesting that high levels of site-specific mechanical loading was advantageous for BMD in females only and a potential presence of reduced energy availability in males. Menstrual status in females and the number of sports completed in childhood in males and females had no influence on bone phenotypes within the runners. CONCLUSION: Given the large variability in BMD in runners and non-athletes, other factors such as variation in genetic make-up alongside mechanical loading probably influence BMD across the adult lifespan.

TTN genotype is associated with fascicle length and marathon running performance.

Titin provides a molecular blueprint for muscle sarcomere assembly, and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus, the aim of this study was to investigate whether the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n=137) and marathon personal best time in male marathon runners (MR; n=141). Fascicle length of the vastus lateralis was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real-time polymerase chain reaction. Vastus lateralis fascicle length was 10.4% longer in CC homozygotes, those carrying two copies of the C-allele, than CT heterozygotes (P=.003) in RA. In the absence of any TT homozygotes, reflective of the low T-allele frequency within Caucasian populations, it is unclear whether fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P=.500), although within the MR group, the T-allele carriers demonstrated marathon personal best times 2 minutes 25 seconds faster than CC homozygotes (P=.020). These results suggest that the T-allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men.

Weight loss and improved metabolic outcomes amongst rural African American women in the Deep South: six-month outcomes from a community-based randomized trial.

BACKGROUND: Obesity is highly prevalent in African American women, especially those in the rural southern USA, resulting in persistent health disparities. OBJECTIVE: To test the effectiveness of an evidence-based behavioural weight loss intervention delivered by community health advisors to African American women in the rural south. DESIGN AND METHODS: Overweight or obese African American women (30-70 years) from eight counties in Mississippi and Alabama participated in a 24-month randomized controlled trial of an evidence-based behavioural weight loss programme augmented with community strategies to support healthy lifestyles (Weight Loss Plus, N = 154) compared to the weight loss programme alone (Weight Loss Only, N = 255). This study reports on 6-month outcomes on primary (weight change) and secondary (waist circumference, blood pressure, lipids, fasting blood glucose) outcomes, coinciding with the completion of the intensive weight loss phase. RESULTS: Weight Loss Only participants lost an average of 2.2 kg (P < 0.001). Weight Loss Plus participants lost an average of 3.2 kg (P < 0.001). The proportion of the total sample that lost at least 5% of their body weight was 27.1% with no difference between treatment groups. Similarly, we observed statistically significant reductions in blood pressure, waist circumference and triglycerides in each treatment group, with no statistical differences between groups. CONCLUSION: Trained lay health staff and volunteers from the rural southern USA were able to deliver a translation of a high-intensity behavioural intervention targeted to African American women, resulting in clinically meaningful weight loss and improvement in other metabolic outcomes in a significant proportion of participants.

Fat mass and obesity associated (FTO) gene influences skeletal muscle phenotypes in non-resistance trained males and elite rugby playing position.

BACKGROUND: FTO gene variants have been associated with obesity phenotypes in sedentary and obese populations, but rarely with skeletal muscle and elite athlete phenotypes. METHODS: In 1089 participants, comprising 530 elite rugby athletes and 559 non-athletes, DNA was collected and genotyped for the FTO rs9939609 variant using real-time PCR. In a subgroup of non-resistance trained individuals (NT; n = 120), we also assessed structural and functional skeletal muscle phenotypes using dual energy x-ray absorptiometry, ultrasound and isokinetic dynamometry. In a subgroup of rugby athletes (n = 77), we assessed muscle power during a countermovement jump. RESULTS: In NT, TT genotype and T allele carriers had greater total body (4.8% and 4.1%) and total appendicular lean mass (LM; 3.0% and 2.1%) compared to AA genotype, with greater arm LM (0.8%) in T allele carriers and leg LM (2.1%) for TT, compared to AA genotype. Furthermore, the T allele was more common (94%) in selected elite rugby union athletes (back three and centre players) who are most reliant on LM rather than total body mass for success, compared to other rugby athletes (82%; P = 0.01, OR = 3.34) and controls (84%; P = 0.03, OR = 2.88). Accordingly, these athletes had greater peak power relative to body mass than other rugby athletes (14%; P = 2 x 10-6). CONCLUSION: Collectively, these results suggest that the T allele is associated with increased LM and elite athletic success. This has implications for athletic populations, as well as conditions characterised by low LM such as sarcopenia and cachexia.

Polymorphisms in PTK2 are associated with skeletal muscle specific force: an independent replication study.

PURPOSE: The aim of the study was to investigate two single nucleotide polymorphisms (SNP) in PTK2 for associations with human muscle strength phenotypes in healthy men. METHODS: Measurement of maximal isometric voluntary knee extension (MVCKE) torque, net MVCKE torque and vastus lateralis (VL) specific force, using established techniques, was completed on 120 Caucasian men (age = 20.6 ± 2.3 year; height = 1.79 ± 0.06 m; mass = 75.0 ± 10.0 kg; mean ± SD). All participants provided either a blood (n = 96) or buccal cell sample, from which DNA was isolated and genotyped for the PTK2 rs7843014 A/C and rs7460 A/T SNPs using real-time polymerase chain reaction. RESULTS: Genotype frequencies for both SNPs were in Hardy-Weinberg equilibrium (X 2 ≤ 1.661, P ≥ 0.436). VL specific force was 8.3% higher in rs7843014 AA homozygotes than C-allele carriers (P = 0.017) and 5.4% higher in rs7460 AA homozygotes than T-allele carriers (P = 0.029). No associations between either SNP and net MVCKE torque (P ≥ 0.094) or peak MVCKE torque (P ≥ 0.107) were observed. CONCLUSIONS: These findings identify a genetic contribution to the inter-individual variability within muscle specific force and provides the first independent replication, in a larger Caucasian cohort, of an association between these PTK2 SNPs and muscle specific force, thus extending our understanding of the influence of genetic variation on the intrinsic strength of muscle.

Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position.

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ(2) and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ(2) = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ(2) = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics.

Potential environmental benefits of prospective genetic changes in broiler traits.

A system approach-based Life Cycle Assessment (LCA) framework, combined with a simple mechanistic model of bird energy balance was used to predict the potential effects of 15 y prospective broiler breeding on the environmental impacts of the standard UK broiler production system. The year 2014 Ross 308 genotype was used as a baseline, and a future scenario was specified from rates of genetic improvement predicted by the industry. The scenario included changes in the traits of growth rate (reducing the time to reach a target weight 2.05 kg from 34 d to 27 d), body lipid content, carcass yield, mortality and the number of chicks produced by a breeder hen. Diet composition was adjusted in order to accommodate the future nutrient requirements of the birds following the genetic change. The results showed that predicted changes in biological performance due to selective breeding could lead to reduced environmental impacts of the broiler production chain, most notably in the Eutrophication Potential (by 12%), Acidification Potential (by 10%) and Abiotic Resource Use (by 9%) and Global Warming Potential (by 9%). These reductions were mainly caused by the reduced maintenance energy requirement and thus lower feed intake, resulting from the shorter production cycle, together with the increased carcass yield. However, some environmental benefits were limited by the required changes in feed composition (e.g., increased inclusion of soy meal and vegetable oil) as a result of the changes in bird nutrient requirements. This study is the first one aiming to link the mechanistic animal modeling approach to predicted genetic changes in order to produce quantitative estimates of the future environmental impacts of broiler production. Although a more detailed understanding on the mechanisms of the potential changes in bird performance and their consequences on feeding and husbandry would be still be needed, the modeling framework produced in this study provides a starting point for predictions of the effects of prospective genetic progress.

The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training.

Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin-I converting enzyme (ACE) and α-actinin-3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (Vm), physiological cross-sectional area (PCSA), maximum isometric force (Ft), specific force (Ft per unit PCSA), maximum isoinertial strength (1-RM), and maximum power (Wmax ; n = 40) before and after 9-week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R-allele carriers had greater Vm, 1-RM, and Wmax than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the "optimal" ACE+ACTN3 genotype combination had greater baseline 1-RM and Wmax compared to those with the "suboptimal" profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human Vm and (independently and in combination with the ACE I/D polymorphism) influences 1-RM and Wmax.

The effects of welfare-enhancing system changes on the environmental impacts of broiler and egg production.

The environmental impacts of 2 alternative UK broiler production systems that aim to improve bird welfare (a lower stocking density indoor system and the same system combined with heat exchangers for ventilation air) were compared with the baseline standard indoor system of broiler production. Furthermore, the environmental impacts of egg production in the conventional battery cage system (banned in the European Union in 2012) and its replacement, the enriched colony cage system, were compared. All comparisons were based on data obtained from the UK poultry industry, and the life cycle assessment method from cradle to farm gate was applied in the analyses. The results show that the lower density system slightly increased the global warming potential (GWP) of broiler production (by 2%), compared with the standard indoor system, due to increased heating requirements. However, when combined with the heat exchanger, the GWP was actually reduced by 3% when compared with the standard system. Both alternative systems for broilers resulted in a reduction in the eutrophication potential (by up to 8%) and acidification potential (by up to 10%). The results also showed that the colony cage system had 8% lower primary energy use and 3% lower GWP than the baseline cage system, due to better energy use efficiency and slightly improved productivity. There were only minor differences in the eutrophication and acidification potentials between different egg production systems. The results suggest that welfare-friendly changes in chicken systems can be achieved without a compromise in their environmental impacts.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations. RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

Passive stiffness of the gastrocnemius muscle in athletes with spastic hemiplegic cerebral palsy.

The passive properties of the muscle-tendon unit are regularly assessed in individuals with cerebral palsy (CP). However, no information is available on the passive properties of adult muscle, and whether any differences exist between the paretic and control muscles. Eleven ambulant male athletes with spastic hemiplegic CP (21.2 ± 3.0 years) and controls without neurological impairment (age = 21.8 ± 2.2 years) completed two and one passive stretch session, respectively. During each session, the ankle was passively dorsiflexed until end range of motion (ROM), whilst recording passive ankle angle, torque and gastrocnemius medialis (GM) myotendinous junction (MTJ) displacement. In addition, GM cross-sectional area (CSA) and length were measured. Subsequently, in vivo stress and strain were determined to calculate elastic modulus. Passive stiffness, MTJ displacement and ROM of the paretic GM were not different from the control muscles. However, the elastic modulus of the paretic GM was two times stiffer than the control GM muscles. In conclusion, athletes with CP exhibit absolute passive muscle stiffness similar to the controls; however, the elastic modulus of the CP muscle was significantly greater. Therefore, throughout the same ROM a smaller GM CSA in CP athletes has to dissipate larger relative torque compared to the control muscles, consequently causing the muscle to elongate to the same extent as the non-paretic muscle under stretch.

Graphene-Based Materials in Dental Applications: Antibacterial, Biocompatible, and Bone Regenerative Properties.

Graphene-based materials have been shown to have advantageous properties in biomedical and dental applications due to their high mechanical, physiochemical, antibacterial, and stem cell differentiating properties. Although graphene-based materials have displayed appropriate biocompatible properties when used in implant materials for orthopedic applications, little research has been performed to specifically test the biocompatibility of graphene for dental applications. The oral environment, compared to the body, varies greatly and must be considered when evaluating biocompatibility requirements for dental applications. This review will discuss in vitro and in vivo studies that assess graphene's cytotoxicity, antibacterial properties, and cell differentiation ability to evaluate the overall biocompatibility of graphene-based materials for dental applications. Particle shape, size, and concentration were found to be major factors that affected overall biocompatibility of graphene.

Predicting the environmental impacts of chicken systems in the United Kingdom through a life cycle assessment: broiler production systems.

The aim of this study was to apply the life cycle assessment (LCA) method, from cradle to gate, to quantify the environmental burdens per 1,000 kg of expected edible carcass weight in the 3 main broiler production systems in the United Kingdom: 1) standard indoor, 2) free range, and 3) organic, and to identify the main components of these burdens. The LCA method evaluates production systems logically to account for all inputs and outputs that cross a specified system boundary, and it relates these to the useful outputs. The analysis was based on an approach that applied a structural model for the UK broiler industry and mechanistic submodels for animal performance, crop production, and major nutrient flows. Simplified baseline feeds representative of those used by the UK broiler industry were used. Typical UK figures for performance and mortality of birds and farm energy and material use were applied. Monte Carlo simulations were used to quantify the uncertainties in the outputs. The length of the production cycle was longer for free-range and organic systems compared with that of the standard indoor system, and as a result, the feed consumption and manure production per bird were higher in the free-range and organic systems. These differences had a major effect on the differences in environmental burdens between the systems. Feed production, processing, and transport resulted in greater overall environmental impacts than any other components of broiler production; for example, 65 to 81% of the primary energy use and 71 to 72% of the global warming potential of the system were due to these burdens. Farm gas and oil use had the second highest impact in primary energy use (12-25%) followed by farm electricity use. The direct use of gas, oil, and electricity were generally lower in free-range and organic systems compared with their use in the standard indoor system. Manure was the main component of acidification potential and also had a relatively high eutrophication potential. The LCA method allows for comparisons between systems and for the identification of hotspots of environmental impacts that could be subject to mitigation.

Predicting the environmental impacts of chicken systems in the United Kingdom through a life cycle assessment: egg production systems.

The aim of this study was to apply a life cycle assessment (LCA) method, from cradle to gate, to quantify the environmental burdens per 1,000 kg of eggs produced in the 4 major hen-egg production systems in the United Kingdom: 1) cage, 2) barn, 3) free range, and 4) organic. The analysis was based on an approach that applied a structural model for the industry and mechanistic submodels for animal performance, crop production, and nutrient flows. Baseline feeds representative of those used by the UK egg production industry were used. Typical figures from the UK egg production industry, feed intake, mortality of birds, farm energy, and material use in different systems were applied. Monte Carlo simulations were used to quantify the uncertainties in the outputs and allow for comparisons between the systems. The number of birds required to produce 1,000 kg of eggs was highest in the organic and lowest in the cage system; similarly, the amount of feed consumed per bird was highest in the organic and lowest in the cage system. These general differences in productivity largely affected the differences in the environmental impacts between the systems. Feed production, processing, and transport caused greater impacts compared with those from any other component of production; that is, 54 to 75% of the primary energy use and 64 to 72% of the global warming potential of the systems. Electricity (used mainly for ventilation, automatic feeding, and lighting) had the second greatest impact in primary energy use (16-38%). Gas and oil (used mainly for heating in pullet rearing and incineration of dead layer birds) used 7 to 14% of the total primary energy. Manure had the greatest impact on the acidification and eutrophication potentials of the systems because of ammonia emissions that contributed to both of these potentials and nitrate leaching that only affected eutrophication potential. The LCA method allows for comparisons between systems and for the identification of hotspots of environmental impacts that could be subject to mitigation.

Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.

OBJECTIVES: The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis. METHODS: The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent. RESULTS: None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects. CONCLUSIONS: Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.