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- Jiang, X., et al.
(author)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 4. |
- Fremat, Y., et al.
(author)
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A test field for Gaia Radial velocity catalogue of stars in the South Ecliptic Pole
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 597
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Journal article (peer-reviewed)abstract
- Context. Gaia is a space mission that is currently measuring the five astrometric parameters, as well as spectrophotometry of at least 1 billion stars to G = 20.7 mag with unprecedented precision. The sixth parameter in phase space (i.e., radial velocity) is also measured thanks to medium-resolution spectroscopy that is being obtained for the 150 million brightest stars. During the commissioning phase, two fields, one around each ecliptic pole, have been repeatedly observed to assess and to improve the overall satellite performances, as well as the associated reduction and analysis software. A ground-based photometric and spectroscopic survey was therefore initiated in 2007, and is still running to gather as much information as possible about the stars in these fields. This work is of particular interest to the validation of the radial velocity spectrometer outputs.Aims. The paper presents the radial velocity measurements performed for the Southern targets in the 12-17 R magnitude range on high-to mid-resolution spectra obtained with the GIRAFFE and UVES spectrographs.Methods. Comparison of the South Ecliptic Pole (SEP) GIRAFFE data to spectroscopic templates observed with the HERMES (Mercator in La Palma, Spain) spectrograph enabled a first coarse characterisation of the 747 SEP targets. Radial velocities were then obtained by comparing the results of three different methods.Results. In this paper, we present an initial overview of the targets to be found in the 1 sq. deg SEP region that was observed repeatedly by Gaia ever since its commissioning. In our representative sample, we identified one galaxy, six LMC S-stars, nine candidate chromospherically active stars, and confirmed the status of 18 LMC Carbon stars. A careful study of the 3471 epoch radial velocity measurements led us to identify 145 RV constant stars with radial velocities varying by less than 1 km s(-1). Seventy-eight stars show significant RV scatter, while nine stars show a composite spectrum. As expected, the distribution of the RVs exhibits two main peaks that correspond to Galactic and LMC stars. By combining [Fe/H] and log g estimates, and RV determinations, we identified 203 members of the LMC, while 51 more stars are candidate members.Conclusions. This is the first systematic spectroscopic characterisation of faint stars located in the SEP field. During the coming years, we plan to continue our survey and gather additional high-and mid-resolution data to better constrain our knowledge on key reference targets for Gaia.
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| 5. |
- Huyghe, Jeroen R., et al.
(author)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Journal article (peer-reviewed)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 6. |
- Schmit, Stephanie L, et al.
(author)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 7. |
- Balestra, F., et al.
(author)
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NANOSIL network of excellence-silicon-based nanostructures and nanodevices for long-term nanoelectronics applications
- 2008
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In: Materials Science in Semiconductor Processing. - : Elsevier BV. - 1369-8001 .- 1873-4081. ; 11:5-6, s. 148-159
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Journal article (peer-reviewed)abstract
- NANOSIL Network of Excellence [NANOSIL NoE web site < www.nanosil-noe.eu >], funded by the European Commission in the 7th Framework Programme (ICT-FP7, no 216171), aims at European scale integration of the excellent European research laboratories and their capabilities in order to strengthen scientific and technological excellence in the field of nanoelectronic materials and devices for terascale integrated circuits (ICs), and to disseminating the results in a wide scientific and industrial community. NANOSIL is exploring and assessing the science and technological aspects of nanodevices and operational regimes relevant to the n+4 technology node and beyond. It encompasses projects on nanoscale CMOS and beyond-CMOS. Innovative concepts, technologies and device architectures are proposed-with fabrication down to the finest features, and utilising a wide spectrum of advanced deposition and processing capabilities, extensive characterization and very rigorous device modeling. This work is carried out through a network of joint processing, characterization and modeling platforms. This critical interaction strengthens European integration in nanoelectronics and will speed up technological innovation for the nanoelectronics of the next two to three decades.
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| 8. |
- Dehaes, S., et al.
(author)
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SED for 7 stellar calibrators (Dehaes+, 2011)
- 2011
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In: VizieR Online Data Catalog. ; 353
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Journal article (peer-reviewed)abstract
- This catalogue presents the theoretical spectral energy distributions for 7 stellar calibrators of the ESA Herschel satellite in the wavelength range from 2 to 200 micron. The stellar atmosphere model and theoretical spectrum are generated using the MARCS theoretical stellar atmosphere code (Gustafsson et al., 1975A\ampA....42..407G and further updates; Gustafsson et al. 2003A\ampA...400..709D) and the TURBOSPECTRUM synthetic spectrum code (Plez et al., 1992A\ampA...256..551P). Stellar parameters (and uncertainties thereon) have been derived by Decin et al. (2003A\ampA...400..709D) and are described in the text files added to this catalogue. The line lists used in the spectrum calculation are discussed in Decin (2000, PhD Thesis, Leuven University) and Decin and Eriksson (2007A\ampA...472.1041D). The outermost depth point of the theoretical atmosphere model was taken at log(tau$_lambda$)=-7.2 with lambda being 2.2 micron. The atmosphere model was calculated with a spherically symmetric (parallel for Sirius) geometry, under the assumption of radiative and hydrostatic equilibrium, local thermodynamic equilibrium (LTE) and homogeneous layers. The original theoretical spectrum was calculated at a resolution of Δλ=0.5Å, and then degraded to a resolution of λ/Δλ=5000 applying a gaussian convolution. The wavelength coverage is from 2 to 200 micron. Uncertainties on the theoretical spectrum predictions are discussed in depth in Decin \amp Eriksson (2007A\ampA...472.1041D). Absolute flux calibration is based on Selby (1988A\ampAS...74..127S) K-band (TCS for Sirius) photometry Zero-point is determined on the basis of an ideal ’Vega’, i.e. the K-band photometry of Vega is corrected for a flux excess of 1.29% (cf. Absil et al. 2006A\ampA...452..237A). The determined Selby K-band zeropoint is 4.0517E-10 W/m2/um. The determined TCS K-band zeropoint is 4.4506E-10W/m2/um (for Sirius) The estimated absolute flux uncertainty is 1% These theoretical spectra should be referenced as Decin \amp Eriksson (2007A\ampA...472.1041D). (3 data files).
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| 9. |
- Dehaes, S., et al.
(author)
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Structure of the outer layers of cool standard stars
- 2011
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A107-
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Journal article (peer-reviewed)abstract
- Context. Among late-type red giants, an interesting change occurs in the structure of the outer atmospheric layers as one moves to later spectral types in the Hertzsprung-Russell diagram: a chromosphere is always present, but the coronal emission diminishes and a cool massive wind steps in. Aims. Where most studies have focussed on short-wavelength observations, this article explores the influence of the chromosphere and the wind on long-wavelength photometric measurements. The goal of this study is to assess wether a set of standard near-infrared calibration sources are fiducial calibrators in the far-infrared, beyond 50 mu m. Methods. The observational spectral energy distributions were compared with the theoretical model predictions for a sample of nine K- and M-giants. The discrepancies found are explained using basic models for flux emission originating in a chromosphere or an ionised wind. Results. For seven out of nine sample stars, a clear flux excess is detected at (sub)millimetre and/or centimetre wavelengths, while only observational upper limits are obtained for the other two. The precise start of the excess depends upon the star under consideration. For six sources the flux excess starts beyond 210 mu m and they can be considered as fiducial calibrators for Herschel/PACS (60-210 mu m). Out of this sample, four sources show no flux excess in the Herschel/SPIRE wavelength range (200-670 mu m) and are good calibration sources for this instrument as well. The flux at wavelengths shorter than similar to 1 mm is most likely dominated by an optically thick chromosphere, where an optically thick ionised wind is the main flux contributor at longer wavelengths. Conclusions. Although the optical to mid-infrared spectrum of the studied K- and M-type infrared standard stars is represented well by a radiative equilibrium atmospheric model, a chromosphere and/or ionised stellar wind at higher altitudes dominates the spectrum in the (sub)millimetre and centimetre wavelength ranges. The presence of a flux excess has implications on the role of the stars as fiducial spectrophotometric calibrators in these wavelength ranges.
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| 10. |
- Hrudkova, M., et al.
(author)
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The discovery of a planetary candidate around the evolved low-mass Kepler giant star HD 175370
- 2017
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 464:1, s. 1018-1028
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Journal article (peer-reviewed)abstract
- We report on the discovery of a planetary companion candidate with a minimum mass M sin i = 4.6 +/- 1.0 M-Jupiter orbiting the K2 III giant star HD 175370 (KIC 007940959). This star was a target in our programme to search for planets around a sample of 95 giant stars observed with Kepler. This detection was made possible using precise stellar radial velocity measurements of HD 175370 taken over five years and four months using the coude echelle spectrograph of the 2-m Alfred Jensch Telescope and the fibre-fed echelle spectrograph High Efficiency and Resolution Mercator Echelle Spectrograph of the 1.2-m Mercator Telescope. Our radial velocity measurements reveal a periodic (349.5 +/- 4.5 d) variation with a semi-amplitude K = 133 +/- 25 ms(-1), superimposed on a long-term trend. A low-mass stellar companion with an orbital period of similar to 88 yr in a highly eccentric orbit and a planet in a Keplerian orbit with an eccentricity e = 0.22 are the most plausible explanation of the radial velocity variations. However, we cannot exclude the existence of stellar envelope pulsations as a cause for the low-amplitude radial velocity variations and only future continued monitoring of this system may answer this uncertainty. From Kepler photometry, we find that HD 175370 is most likely a low-mass red giant branch or asymptotic giant branch star.
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