| 2. |
- Dadaev, T, et al.
(författare)
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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| 4. |
- Tomkinson, GR, et al.
(författare)
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European normative values for physical fitness in children and adolescents aged 9-17 years: results from 2 779 165 Eurofit performances representing 30 countries
- 2018
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 52:22, s. 1445-1456
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Tidskriftsartikel (refereegranskat)abstract
- To develop sex-specific and age-specific normative values for the nine Eurofit tests in European children and adolescents aged 9–17 years.MethodsA systematic review was undertaken to identify papers that explicitly reported descriptive results for at least one of nine Eurofit tests (measuring balance, muscular strength, muscular endurance, muscular power, flexibility, speed, speed-agility and cardiorespiratory fitness (CRF)) on children and adolescents. Data were included on apparently healthy (free from known disease/injury) children and adolescents aged 9–17 years. Following harmonisation for methodological variation where appropriate, pseudodata were generated using Monte Carlo simulation, with population-weighted sex-specific and age-specific normative centiles generated using the Lambda Mu Sigma (LMS) method. Sex-specific and age-specific differences were expressed as standardised differences in means, with the percentage of children and adolescents with healthy CRF estimated at the sex-age level.ResultsNorms were displayed as tabulated centiles and as smoothed centile curves for the nine Eurofit tests. The final dataset included 2 779 165 results on children and adolescents from 30 European countries, extracted from 98 studies. On average, 78% of boys (95% CI 72% to 85%) and 83% of girls (95% CI 71% to 96%) met the standards for healthy CRF, with the percentage meeting the standards decreasing with age. Boys performed substantially (standardised differences >0.2) better than girls on muscular strength, muscular power, muscular endurance, speed-agility and CRF tests, but worse on the flexibility test. Physical fitness generally improved at a faster rate in boys than in girls, especially during the teenage years.ConclusionThis study provides the largest and most geographically representative sex-specific and age-specific European normative values for children and adolescents, which have utility for health and fitness screening, profiling, monitoring and surveillance.
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