| 1. |
- Aghanim, N., et al.
(author)
-
Planck intermediate results XLVI. Reduction of large-scale systematic effects in HFI polarization maps and estimation of the reionization optical depth
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
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Journal article (peer-reviewed)abstract
- This paper describes the identification, modelling, and removal of previously unexplained systematic effects in the polarization data of the Planck High Frequency Instrument (HFI) on large angular scales, including new mapmaking and calibration procedures, new and more complete end-to-end simulations, and a set of robust internal consistency checks on the resulting maps. These maps, at 100, 143, 217, and 353 GHz, are early versions of those that will be released in final form later in 2016. The improvements allow us to determine the cosmic reionization optical depth tau using, for the first time, the low-multipole EE data from HFI, reducing significantly the central value and uncertainty, and hence the upper limit. Two different likelihood procedures are used to constrain tau from two estimators of the CMB E- and B-mode angular power spectra at 100 and 143 GHz, after debiasing the spectra from a small remaining systematic contamination. These all give fully consistent results. A further consistency test is performed using cross-correlations derived from the Low Frequency Instrument maps of the Planck 2015 data release and the new HFI data. For this purpose, end-to-end analyses of systematic effects from the two instruments are used to demonstrate the near independence of their dominant systematic error residuals. The tightest result comes from the HFI-based tau posterior distribution using the maximum likelihood power spectrum estimator from EE data only, giving a value 0.055 +/- 0.009. In a companion paper these results are discussed in the context of the best-fit Planck Lambda CDM cosmological model and recent models of reionization.
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| 2. |
- Adam, R., et al.
(author)
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Planck intermediate results XLVII. Planck constraints on reionization history
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
-
Journal article (peer-reviewed)abstract
- We investigate constraints on cosmic reionization extracted from the Planck cosmic microwave background (CMB) data. We combine the Planck CMB anisotropy data in temperature with the low-multipole polarization data to fit Lambda CDM models with various parameterizations of the reionization history. We obtain a Thomson optical depth tau = 0.058 +/- 0.012 for the commonly adopted instantaneous reionization model. This confirms, with data solely from CMB anisotropies, the low value suggested by combining Planck 2015 results with other data sets, and also reduces the uncertainties. We reconstruct the history of the ionization fraction using either a symmetric or an asymmetric model for the transition between the neutral and ionized phases. To determine better constraints on the duration of the reionization process, we also make use of measurements of the amplitude of the kinetic Sunyaev-Zeldovich (kSZ) effect using additional information from the high-resolution Atacama Cosmology Telescope and South Pole Telescope experiments. The average redshift at which reionization occurs is found to lie between z = 7.8 and 8.8, depending on the model of reionization adopted. Using kSZ constraints and a redshift-symmetric reionization model, we find an upper limit to the width of the reionization period of Delta z < 2.8. In all cases, we find that the Universe is ionized at less than the 10% level at redshifts above z similar or equal to 10. This suggests that an early onset of reionization is strongly disfavoured by the Planck data. We show that this result also reduces the tension between CMB-based analyses and constraints from other astrophysical sources.
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| 3. |
- Aghanim, N., et al.
(author)
-
Planck intermediate results XLIX. Parity-violation constraints from polarization data
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
-
Journal article (peer-reviewed)abstract
- Parity-violating extensions of the standard electromagnetic theory cause in vacuo rotation of the plane of polarization of propagating photons. This effect, also known as cosmic birefringence, has an impact on the cosmic microwave background (CMB) anisotropy angular power spectra, producing non-vanishing T-B and E-B correlations that are otherwise null when parity is a symmetry. Here we present new constraints on an isotropic rotation, parametrized by the angle alpha, derived from Planck 2015 CMB polarization data. To increase the robustness of our analyses, we employ two complementary approaches, in harmonic space and in map space, the latter based on a peak stacking technique. The two approaches provide estimates for alpha that are in agreement within statistical uncertainties and are very stable against several consistency tests. Considering the T-B and E-B information jointly, we find alpha = 0 degrees: 31 +/- 0 degrees.05 (stat:) +/- 0 degrees:28 (syst:) from the harmonic analysis and alpha = 0 degrees.35 +/- 0 degrees.05 (stat :) 0 degrees.28 (syst :) from the stacking approach. These constraints are compatible with no parity violation and are dominated by the systematic uncertainty in the orientation of Planck's polarization-sensitive bolometers.
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| 4. |
- Aghanim, N., et al.
(author)
-
Planck intermediate results LI. Features in the cosmic microwave background temperature power spectrum and shifts in cosmological parameters
- 2017
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 607
-
Journal article (peer-reviewed)abstract
- The six parameters of the standard Lambda CDM model have best-fit values derived from the Planck temperature power spectrum that are shifted somewhat from the best-fit values derived from WMAP data. These shifts are driven by features in the Planck temperature power spectrum at angular scales that had never before been measured to cosmic-variance level precision. We have investigated these shifts to determine whether they are within the range of expectation and to understand their origin in the data. Taking our parameter set to be the optical depth of the reionized intergalactic medium tau, the baryon density omega(b), the matter density omega(m), the angular size of the sound horizon theta(*), the spectral index of the primordial power spectrum, n(s), and A(s)e(-2 pi) (where As is the amplitude of the primordial power spectrum), we have examined the change in best-fit values between a WMAP-like large angular-scale data set (with multipole moment l < 800 in the Planck temperature power spectrum) and an all angular-scale data set (l < 2500 Planck temperature power spectrum), each with a prior on tau of 0.07 +/- 0.02. We find that the shifts, in units of the 1 sigma expected dispersion for each parameter, are {Delta tau, Delta A(s)e(-2 tau), Delta n(s), Delta omega(m), Delta omega(b), Delta theta(*)} = {-1.7, -2.2, 1.2, 2.0, 1.1, 0.9}, with a chi(2) value of 8.0. We find that this chi(2) value is exceeded in 15% of our simulated data sets, and that a parameter deviates by more than 2.2 sigma in 9% of simulated data sets, meaning that the shifts are not unusually large. Comparing l < 800 instead to l > 800, or splitting at a different multipole, yields similar results. We examined the l < 800 model residuals in the l > 800 power spectrum data and find that the features there that drive these shifts are a set of oscillations across a broad range of angular scales. Although they partly appear similar to the effects of enhanced gravitational lensing, the shifts in Lambda CDM parameters that arise in response to these features correspond to model spectrum changes that are predominantly due to non-lensing effects; the only exception is tau, which, at fixed A(s)e(-2 tau), affects the l > 800 temperature power spectrum solely through the associated change in As and the impact of that on the lensing potential power spectrum. We also ask, what is it about the power spectrum at l < 800 that leads to somewhat different best-fit parameters than come from the full l range? We find that if we discard the data at l < 30, where there is a roughly 2 sigma downward fluctuation in power relative to the model that best fits the full l range, the l < 800 best-fit parameters shift significantly towards the l < 2500 best-fit parameters. In contrast, including l < 30, this previously noted low-l deficit drives ns up and impacts parameters correlated with ns, such as omega(m) and H-0. As expected, the l < 30 data have a much greater impact on the l < 800 best fit than on the l < 2500 best fit. So although the shifts are not very significant, we find that they can be understood through the combined effects of an oscillatory-like set of high-l residuals and the deficit in low-l power, excursions consistent with sample variance that happen to map onto changes in cosmological parameters. Finally, we examine agreement between Planck TT data and two other CMB data sets, namely the Planck lensing reconstruction and the TT power spectrum measured by the South Pole Telescope, again finding a lack of convincing evidence of any significant deviations in parameters, suggesting that current CMB data sets give an internally consistent picture of the Lambda CDM model.
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| 5. |
- Aghanim, N., et al.
(author)
-
Planck intermediate results LIII. Detection of velocity dispersion from the kinetic Sunyaev-Zeldovich effect
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
-
Journal article (peer-reviewed)abstract
- Using the Planck full-mission data, we present a detection of the temperature (and therefore velocity) dispersion due to the kinetic Sunyaev-Zeldovich (kSZ) effect from clusters of galaxies. To suppress the primary CMB and instrumental noise we derive a matched filter and then convolve it with the Planck foreground-cleaned 2D- ILC maps. By using the Meta Catalogue of X-ray detected Clusters of galaxies (MCXC), we determine the normalized rms dispersion of the temperature fluctuations at the positions of clusters, finding that this shows excess variance compared with the noise expectation. We then build an unbiased statistical estimator of the signal, determining that the normalized mean temperature dispersion of 1526 clusters is <(Delta T/T)(2))> = (1.64 +/- 0.48) x 10(-11). However, comparison with analytic calculations and simulations suggest that around 0.7 sigma of this result is due to cluster lensing rather than the kSZ effect. By correcting this, the temperature dispersion is measured to be <(Delta T/T)(2))> = (1.35 +/- 0.48) x 10(-11), which gives a detection at the 2.8 sigma level. We further convert uniform-weight temperature dispersion into a measurement of the line-of-sight velocity dispersion, by using estimates of the optical depth of each cluster (which introduces additional uncertainty into the estimate). We find that the velocity dispersion is (v(2)) = (123 000 +/- 71 000) (km s(-1))(2), which is consistent with findings from other large-scale structure studies, and provides direct evidence of statistical homogeneity on scales of 600 h(-1) Mpc. Our study shows the promise of using cross-correlations of the kSZ effect with large-scale structure in order to constrain the growth of structure.
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| 6. |
- Aghanim, N., et al.
(author)
-
Planck intermediate results XLVIII. Disentangling Galactic dust emission and cosmic infrared background anisotropies
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
-
Journal article (peer-reviewed)abstract
- Using the Planck 2015 data release (PR2) temperature maps, we separate Galactic thermal dust emission from cosmic infrared background (CIB) anisotropies. For this purpose, we implement a specifically tailored component-separation method, the so-called generalized needlet internal linear combination (GNILC) method, which uses spatial information (the angular power spectra) to disentangle the Galactic dust emission and CIB anisotropies. We produce significantly improved all-sky maps of Planck thermal dust emission, with reduced CIB contamination, at 353, 545, and 857 GHz. By reducing the CIB contamination of the thermal dust maps, we provide more accurate estimates of the local dust temperature and dust spectral index over the sky with reduced dispersion, especially at high Galactic latitudes above b = +/- 20 degrees. We find that the dust temperature is T = (19.4 +/- 1.3) K and the dust spectral index is beta = 1.6 +/- 0.1 averaged over the whole sky, while T = (19.4 +/- 1.5) K and beta = 1.6 +/- 0.2 on 21% of the sky at high latitudes. Moreover, subtracting the new CIB-removed thermal dust maps from the CMB-removed Planck maps gives access to the CIB anisotropies over 60% of the sky at Galactic latitudes vertical bar b vertical bar > 20 degrees. Because they are a significant improvement over previous Planck products, the GNILC maps are recommended for thermal dust science. The new CIB maps can be regarded as indirect tracers of the dark matter and they are recommended for exploring cross-correlations with lensing and large-scale structure optical surveys. The reconstructed GNILC thermal dust and CIB maps are delivered as Planck products.
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| 7. |
- Akrami, Y., et al.
(author)
-
Planck intermediate results LIV. The Planck multi-frequency catalogue of non-thermal sources
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 619
-
Journal article (peer-reviewed)abstract
- This paper presents the Planck Multi-frequency Catalogue of Non-thermal (i.e. synchrotron-dominated) Sources (PCNT) observed between 30 and 857 GHz by the ESA Planck mission. This catalogue was constructed by selecting objects detected in the full mission all-sky temperature maps at 30 and 143 GHz, with a signal-to-noise ratio (S/N) > 3 in at least one of the two channels after filtering with a particular Mexican hat wavelet. As a result, 29 400 source candidates were selected. Then, a multi-frequency analysis was performed using the Matrix Filters methodology at the position of these objects, and flux densities and errors were calculated for all of them in the nine Planck channels. This catalogue was built using a different methodology than the one adopted for the Planck Catalogue of Compact Sources (PCCS) and the Second Planck Catalogue of Compact Sources (PCCS2), although the initial detection was done with the same pipeline that was used to produce them. The present catalogue is the first unbiased, full-sky catalogue of synchrotron-dominated sources published at millimetre and submillimetre wavelengths and constitutes a powerful database for statistical studies of non-thermal extragalactic sources, whose emission is dominated by the central active galactic nucleus. Together with the full multi-frequency catalogue, we also define the Bright Planck Multi-frequency Catalogue of Non-thermal Sources (PCNTb), where only those objects with a S/N > 4 at both 30 and 143 GHz were selected. In this catalogue 1146 compact sources are detected outside the adopted Planck GAL070 mask; thus, these sources constitute a highly reliable sample of extragalactic radio sources. We also flag the high-significance subsample (PCNThs), a subset of 151 sources that are detected with S/N > 4 in all nine Planck channels, 75 of which are found outside the Planck mask adopted here. The remaining 76 sources inside the Galactic mask are very likely Galactic objects.
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| 8. |
- Burigana, C., et al.
(author)
-
Exploring cosmic origins with CORE : Effects of observer peculiar motion
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- We discuss the effects on the cosmic microwave background (CMB), cosmic infrared background (CIB), and thermal Sunyaev-Zeldovich effect due to the peculiar motion of an observer with respect to the CMB rest frame, which induces boosting effects. After a brief review of the current observational and theoretical status, we investigate the scientific perspectives opened by future CMB space missions, focussing on the Cosmic Origins Explorer (CORE) proposal. The improvements in sensitivity offered by a mission like CORE, together with its high resolution over a wide frequency range, will provide a more accurate estimate of the CMB dipole. The extension of boosting effects to polarization and cross-correlations will enable a more robust determination of purely velocity-driven effects that are not degenerate with the intrinsic CMB dipole, allowing us to achieve an overall signal-to-noise ratio of 13; this improves on the Planck detection and essentially equals that of an ideal cosmic variance-limited experiment up to a multipole l similar or equal to 2000. Precise inter-frequency calibration will offer the opportunity to constrain or even detect CMB spectral distortions, particularly from the cosmological reionization epoch, because of the frequency dependence of the dipole spectrum, without resorting to precise absolute calibration. The expected improvement with respect to COBE-FIRAS in the recovery of distortion parameters (which could in principle be a factor of several hundred for an ideal experiment with the CORE configuration) ranges from a factor of several up to about 50, depending on the quality of foreground removal and relative calibration. Even in the case of similar or equal to 1% accuracy in both foreground removal and relative calibration at an angular scale of 1 degrees, we find that dipole analyses for a mission like CORE will be able to improve the recovery of the CIB spectrum amplitude by a factor similar or equal to 17 in comparison with current results based on COBE-FIRAS. In addition to the scientific potential of a mission like CORE for these analyses, synergies with other planned and ongoing projects are also discussed.
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| 9. |
- Delabrouille, J., et al.
(author)
-
Exploring cosmic origins with CORE : Survey requirements and mission design
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology, including: what physical process gave birth to the Universe we see today? What are the dark matter and dark energy that seem to constitute 95% of the energy density of the Universe? Do we need extensions to the standard model of particle physics and fundamental interactions? Is the ACDM cosmological scenario correct, or are we missing an essential piece of the puzzle? In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the CORE space mission proposed to ESA in answer to the M5 call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. CORE has 19 frequency channels, distributed over a broad frequency range, spanning the 60-600 GHz interval, to control astrophysical foreground emission. The angular resolution ranges from 2' to 18', and the aggregate CMB sensitivity is about 2 mu K.arcmin. The observations are made with a single integrated focal-plane instrument, consisting of an array of 2100 cryogenically-cooled, linearly-polarised detectors at the focus of a 1.2-m aperture cross-Dragone telescope. The mission is designed to minimise all sources of systematic effects, which must be controlled so that no more than 10(-4) of the intensity leaks into polarisation maps, and no more than about 1% of E-type polarisation leaks into B-type modes. CORE observes the sky from a large Lissajous orbit around the Sun-Earth L2 point on an orbit that offers stable observing conditions and avoids contamination from sidelobe pick-up of stray radiation originating from the Sun, Earth, and Moon. The entire sky is observed repeatedly during four years of continuous scanning, with a combination of three rotations of the spacecraft over different timescales. With about 50% of the sky covered every few days, this scan strategy provides the mitigation of systematic effects and the internal redundancy that are needed to convincingly extract the primordial B-mode signal on large angular scales, and check with adequate sensitivity the consistency of the observations in several independent data subsets. CORE is designed as a near-ultimate CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation science and cannot be obtained by any other means than a dedicated space mission. It will provide well-characterised, highly-redundant multi-frequency observations of polarisation at all the scales where foreground emission and cosmic variance dominate the final uncertainty for obtaining precision CMB science, as well as 2' angular resolution maps of high-frequency foreground emission in the 300-600 GHz frequency range, essential for complementarity with future ground-based observations with large telescopes that can observe the CMB with the same beamsize.
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| 10. |
- Finelli, F., et al.
(author)
-
Exploring cosmic origins with CORE : Inflation
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2018:4
-
Journal article (peer-reviewed)abstract
- We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 mu K.arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series Exploring Cosmic Origins with CORE. We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10(-3) level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10(-3) level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the f(NL)(local) < 1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.
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| 11. |
- Challinor, A., et al.
(author)
-
Exploring cosmic origins with CORE : Gravitational lensing of the CMB
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-SAN modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can delens the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.
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| 12. |
- De Zotti, G., et al.
(author)
-
Exploring cosmic origins with CORE : Extragalactic sources in cosmic microwave background maps
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- We discuss the potential of a next generation space-borne Cosmic Microwave Background (CMB) experiment for studies of extragalactic sources. Our analysis has particular bearing on the definition of the future space project, CORE, that has been submitted in response to ESA's call for a Medium-size mission opportunity as the successor of the Planck satellite. Even though the effective telescope size will be somewhat smaller than that of Planck, CORE will have a considerably better angular resolution at its highest frequencies, since, in contrast with Planck, it will be diffraction limited at all frequencies. The improved resolution implies a considerable decrease of the source confusion, i.e. substantially fainter detection limits. In particular, CORE will detect thousands of strongly lensed high-z galaxies distributed over the full sky. The extreme brightness of these galaxies will make it possible to study them, via follow-up observations, in extraordinary detail. Also, the CORE resolution matches the typical sizes of high-z galaxy proto-clusters much better than the Planck resolution, resulting in a much higher detection efficiency; these objects will be caught in an evolutionary phase beyond the reach of surveys in other wavebands. Furthermore, CORE will provide unique information on the evolution of the star formation in virialized groups and clusters of galaxies up to the highest possible redshifts. Finally, thanks to its very high sensitivity, CORE will detect the polarized emission of thousands of radio sources and, for the first time, of dusty galaxies, at mm and sub-mm wavelengths, respectively.
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| 13. |
- Di Valentino, E., et al.
(author)
-
Exploring cosmic origins with CORE : Cosmological parameters
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume ACDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base ACDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. In addition to assessing the improvement on the precision of individual parameters, we also forecast the post-CORE overall reduction of the allowed parameter space with figures of merit for various models increasing by as much as similar to 10(7) as compared to Planck 2015, and 10(5) with respect to Planck 2015 + future BAO measurements.
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| 14. |
- Natoli, P., et al.
(author)
-
Exploring cosmic origins with CORE : Mitigation of systematic effects
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.
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| 15. |
- Remazeilles, M., et al.
(author)
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Exploring cosmic origins with CORE : B-mode component separation
- 2018
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
-
Journal article (peer-reviewed)abstract
- We demonstrate that, for the baseline design of the CORE satellite mission, the polarized foregrounds can be controlled at the level required to allow the detection of the primordial cosmic microwave background (CMB) B-mode polarization with the desired accuracy at both reionization and recombination scales, for tensor-to-scalar ratio values of r greater than or similar to 5 x 10(-3). We consider detailed sky simulations based on state-of-the-art CMB observations that consist of CMB polarization with tau = 0.055 and tensor-to-scalar values ranging from r = 10(-2) to 10(-3), Galactic synchrotron, and thermal dust polarization with variable spectral indices over the sky, polarized anomalous microwave emission, polarized infrared and radio sources, and gravitational lensing effects. Using both parametric and blind approaches, we perform full component separation and likelihood analysis of the simulations, allowing us to quantify both uncertainties and biases on the reconstructed primordial B-modes. Under the assumption of perfect control of lensing effects, CORE would measure an unbiased estimate of r = (5 +/- 0.4) x 10(-3) after foreground cleaning. In the presence of both gravitational lensing effects and astrophysical foregrounds, the significance of the detection is lowered, with CORE achieving a 4 sigma-measurement of r = 5 x 10(-3) after foreground cleaning and 60% de lensing. For lower tensor-to-scalar ratios (r = 10(-3)) the overall uncertainty on r is dominated by foreground residuals, not by the 40% residual of lensing cosmic variance. Moreover, the residual contribution of unprocessed polarized point-sources can be the dominant foreground contamination to primordial B-modes at this r level, even on relatively large angular scales, l similar to 50. Finally, we report two sources of potential bias for the detection of the primordial B-modes by future CMB experiments: (i) the use of incorrect foreground models, e.g. a modelling error of Delta beta(s) = 0.02 on the synchrotron spectral indices may result in an excess in the recovered reionization peak corresponding to an effective Delta r > 10(-3); (ii) the average of the foreground line-of-sight spectral indices by the combined effects of pixelization and beam convolution, which adds an effective curvature to the foreground spectral energy distribution and may cause spectral degeneracies with the CMB in the frequency range probed by the experiment.
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| 16. |
- Figueroa, Jonine D., et al.
(author)
-
Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry
- 2016
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 25:6, s. 1203-1214
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Journal article (peer-reviewed)abstract
- Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
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| 17. |
- Machiela, Mitchell J, et al.
(author)
-
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 18. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 19. |
- Clendenen, Tess V., et al.
(author)
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Breast cancer risk prediction in women aged 35-50 years : impact of including sex hormone concentrations in the Gail model
- 2019
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In: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 21
-
Journal article (peer-reviewed)abstract
- Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
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| 20. |
- Ge, Wenzhen, et al.
(author)
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Circulating anti-Müllerian hormone and breast cancer risk : a study in ten prospective cohorts
- 2018
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In: International Journal of Cancer. - Hoboken : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:11, s. 2215-2226
-
Journal article (peer-reviewed)abstract
- A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.
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| 21. |
- 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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| 22. |
- Lang Kuhs, Krystle A, et al.
(author)
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Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer : A Pooled Analysis
- 2015
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 24:4, s. 683-689
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.
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| 23. |
- Machiela, Mitchell J., et al.
(author)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
-
Journal article (peer-reviewed)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 24. |
- Miguel, Sophie, et al.
(author)
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Poor cognitive ageing : Vulnerabilities, mechanisms and the impact of nutritional interventions
- 2018
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 42, s. 40-55
-
Research review (peer-reviewed)abstract
- Background: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated.Objectives: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe).Conclusion: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.
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| 25. |
-
RRI implementation in bioscience organisations : Guidelines from the STARBIOS2 project
- 2019
-
Editorial collection (peer-reviewed)abstract
- The Guidelines are a tool to promote, within biosciences research organisations, a structural change (i.e., a durable transformation of a research organisation) that facilitates the practice of Responsible Research and Innovation (RRI). They are one of the outputs of the STARBIOS2 project.The Guidelines arise from the practical experience of implementing Action Plans carried by the research organisations involved in the STARBIOS2 project, from the mutual learning activity among the STARBIOS2 partners, also supported by a study and update of RRI issues.The Guidelines aim to help readers to formalize and trigger structural change aimed at introducing RRI-related practices that are appropriate to their own organisations. The Guidelines are not a series of prescriptions, but an itinerary of reflection and self-interpretation that is addressed to different actors within the Biosciences, such as: researchers, research organisations managers and technical staff members, professionals within research-funding organisations, students and others. Although these Guidelines are not designed for their specific needs, they could be useful to science policymakers as well. In very general terms, the Guidelines’ readers are people who intend to promote RRI or to emphasize responsibility within the research activities in which they are engaged, or who are trying to collect resources for designing and implementing activities with this end.To support this itinerary of reflection and self-interpretation, the document provides:A description of a general RRI Model for research organisations within the biosciences, that is a set of ideas, premises and “principles of action” that define the practice of RRI in Bioscience research organisationsSome practical guidance for designing interventions to promote RRI in research organisations in the Biosciences, putting into practice the RRI ModelA set of useful practices in implementing the structural change process.Information on particular STARBIOS2 cases and experiences, as well as materials, tools and sources, are also provided in the Appendix and in the Annex.
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| 26. |
- Schmit, Stephanie L, et al.
(author)
-
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
-
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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| 27. |
- Valleix, Sophie, et al.
(author)
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D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.
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| 28. |
- van Roekel, Eline H., et al.
(author)
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Circulating metabolites associated with alcohol intake in the european prospective investigation into cancer and nutrition cohort
- 2018
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 10:5
-
Journal article (peer-reviewed)abstract
- Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTMp180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption withmetabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.
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| 29. |
- Wahl, Simone, et al.
(author)
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Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
- 2017
-
In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-
-
Journal article (peer-reviewed)abstract
- Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
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| 30. |
- Zhang, Mingfeng, et al.
(author)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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