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- 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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- Martinez-Tellez, R, et al.
(författare)
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Association of wrist and ambient temperature with cold-induced brown adipose tissue and skeletal muscle [18F]FDG uptake in young adults
- 2018
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 315:6, s. R1281-R1288
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) activity is influenced by the outdoor temperature variation. However, people spend most of their time indoors, especially in colder regions and during cold seasons. Therefore, outdoor temperature is probably not an accurate tool to quantify the exposure of the participants before BAT quantification. We studied the association of wrist and personal environmental temperatures with cold-induced BAT and skeletal muscle [18F]fluorodeoxyglucose ([18F]FDG) uptake in adults. A total of 74 participants wore two iButtons during 7 days to measure wrist temperature (WT) and personal level of environmental temperature (Personal-ET). Thereafter, we performed a 2-h personalized cooling protocol before performing an [18F]FDG-PET/CT scan. WT was negatively associated with BAT volume ( R2 = 0.122; P = 0.002) and BAT activity [standardized uptake value (SUV)peak, R2 = 0.083; P = 0.012]. Moreover, Personal-ET was negatively associated with BAT volume ( R2 = 0.164; P < 0.001), BAT activity (SUVmean and SUVpeak, all R2 ≥ 0.167; P < 0.001), and skeletal muscle activity (SUVpeak, R2 = 0.122; P = 0.002). Interestingly, the time exposed to a certain Personal-ET (16–20°C) positively correlated only with [18F]FDG uptake by BAT (volume and activity; all P ≤ 0.05), whereas the time exposed to 12–15°C positively correlated only with measures of [18F]FDG uptake by skeletal muscle activity (all P ≤ 0.05). This study shows that WT and Personal-ET are associated with [18F]FDG uptake by BAT and skeletal muscle activity in adults within certain temperature thresholds. Moreover, our results suggest that [18F]FDG uptake by human BAT or skeletal muscle can be activated or inhibited in different ranges of ambient temperatures exposures. Results should be taken with caution because the observed associations were relatively weak.
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- Wang, HD, et al.
(författare)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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