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- Dadaev, T, et al.
(author)
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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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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Journal article (peer-reviewed)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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- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 7. |
- Wang, Anqi, et al.
(author)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Afanaciev, K.G., et al.
(author)
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Investigation of the radiation hardness of GaAs sensors in an electron beam
- 2012
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In: Journal of Instrumentation. - 1748-0221. ; 7:11
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Journal article (peer-reviewed)abstract
- A compact and finely grained sandwich calorimeter is designed to instrument the very forward region of a detector at a future e+e- collider. The calorimeter will be exposed to low energy e+e - pairs originating from beamstrahlung, resulting in absorbed doses of about one MGy per year. GaAs pad sensors interleaved with tungsten absorber plates are considered as an option for this calorimeter. Several Cr-doped GaAs sensor prototypes were produced and irradiated with 8.5-10 MeV electrons up to a dose of 1.5 MGy. The sensor performance was measured as a function of the absorbed dose.
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- Chen, C., et al.
(author)
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A gigabit transceiver for the ATLAS inner tracker pixel detector readout upgrade
- 2019
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In: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 14
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Journal article (peer-reviewed)abstract
- This paper presents the design and simulation results of a gigabit transceiver Application Specific Integrated Circuit (ASIC) called GBCR for the ATLAS Inner Tracker (ITk) Pixel detector readout upgrade. GBCR has four upstream receiver channels and a downstream transmitter channel. Each upstream channel operates at 5.12 Gbps, while the downstream channel operates at 2.56 Gbps. In each upstream channel, GBCR equalizes a signal received through a 5-meter 34-American Wire Gauge (AWG) twin-axial cable, retimes the data with a recovered clock, and drives an optical transmitter. In the downstream channel, GBCR receives the data from an optical receiver and drives the same type of cable as the upstream channels. The output jitter of an upstream channel is 26.5 ps and the jitter of the downstream channel after the cable is 33.5 ps. Each upstream channel consumes 78 mW and each downstream channel consumes 27 mW. Simulation results of the upstream test channel suggest that a significant jitter reduction could be achieved with minimally increased power consumption by using a Feed Forward Equalizer (FFE) + Decision Feedback Equalization (DFE) in addition to the linear equalization of the baseline channel. GBCR is designed in a 65-nm CMOS technology.
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- De Gaspari, Massimiliano, et al.
(author)
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Design of the analog front-end for the Timepix3 and Smallpix hybrid pixel detectors in 130 nm CMOS technology
- 2014
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In: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 9, s. Art. no. C01037-
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Journal article (peer-reviewed)abstract
- This paper describes a front-end for hybrid pixel readout chips, which was developed for the Timepix3 and Smallpix ASICs. The front-end contains a single-ended preamplifier with a structure for leakage current compensation which can handle both signal polarities, and a single-threshold discriminator with compensation for pixel-to-pixel mismatch. Preamplifier and discriminator are required to be fast, to allow a Time-Of-Arrival (TOA) measurement with a resolution of 1.56 ns. Time-Over-Threshold (TOT) is also measured; the monotonicity of TOT with respect to the input charge is greatly improved as compared to the previous Timepix chip. The analog area is only 55 μm × 13.5 μm. Timepix3 has already been fabricated and the first test results are also presented in this paper.
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