Clinical Trial Service Unit

About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.

Improved prediction of fracture risk leveraging a genome-wide polygenic risk score

Abstract: Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction. We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors. A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072. We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.

Advances in Stroke 2017.

Abstract: For stroke rehabilitation and recovery, 2017 was a year of reviews and research advances. Reviews included all aspects of poststroke rehabilitation and recovery. Cognitive rehabilitation for memory deficits was effective for memory improvements in the short term, but not in the long term.1 Circuit class therapy could improve mobility after stroke in a clinically meaningful way, even after 12 months poststroke.2 Electromechanical-assisted training for walking was most beneficial for subacute stroke survivors who were not ambulatory.3 Repetitive task training was effective regardless of the amount of task practice, type of intervention, or time since stroke.4 Physical activity training could positively affect poststroke cognition with small-to-moderate treatment effects that were apparent even in the chronic stroke phase.5 In all cases, more research was required to improve the quality of the findings, and a review of poststroke fatigue reported that the overall quality of the research was poor.6 Discovery research provided more insight into basic aspects of stroke rehabilitation and recovery. Stradecki-Cohan et al7 studied Sprague–Dawley rats subjected to 5 to 6 days of no (0 m/min), mild (6 m/min), moderate (10 m/min), or heavy (15–18 m/min) treadmill exercise 3 to 4 days poststroke and demonstrated that moderate exercise enhanced cognitive function for 1 week after exercise completion, independent of changes in physical fitness. Chang et al8 demonstrated that the number of Met alleles in brain-derived neurotrophic factor genotypes and corticospinal tract (CST) functional integrity may be independent predictors of upper extremity motor outcome 3 months poststroke. Tu et al9 found that concentrations of FABP4 (fatty acid–binding protein 4), an intracellular lipid chaperone involved in coordination of lipid transportation and atherogenesis, were a novel independent prognostic marker for poor functional outcome and mortality 3 months poststroke. Imaging of the CST also played a …

A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic aetiology with obesity.

Abstract: Background Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWASs in other populations are lacking. Methods We included 100 285 subjects from the China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS analyses were performed on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in the CKB. We then performed genome-wide cross-trait analysis between lung function and obesity traits (body mass index (BMI), BMI-adjusted waist-to-hip ratio and BMI-adjusted waist circumference) to investigate the shared genetic effects in the CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in the CKB and their interaction with BMI9s association on lung function were examined. We also conducted cross-trait analysis in parallel with the CKB using up to 457 756 subjects from the UK Biobank (UKB) for replication and investigation of ancestry-specific effects. Results We identified nine genome-wide significant novel loci for FEV1, six for FVC and three for FEV1/FVC in the CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both the CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important biological pathways, including cell proliferation, embryo, skeletal and tissue development, and regulation of gene expression. Mendelian randomisation analysis suggested significant negative causal effects of BMI on FEV1 and on FVC in both the CKB and UKB. Lung function PRSs significantly modified the effect of change in BMI on change in lung function during an average follow-up of 8 years. Conclusion This large-scale GWAS of lung function identified novel loci and shared genetic aetiology between lung function and obesity. Change in BMI might affect change in lung function differently according to a subject9s polygenic background. These findings may open new avenues for the development of molecular-targeted therapies for obesity and lung function improvement.