| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Hsiao, E. Y., et al.
(författare)
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Carnegie Supernova Project-II : The Near-infrared Spectroscopy Program
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- Shifting the focus of Type Ia supernova (SN Ia) cosmology to the near infrared (NIR) is a promising way to significantly reduce the systematic errors, as the strategy minimizes our reliance on the empirical width-luminosity relation and uncertain dust laws. Observations in the NIR are also crucial for our understanding of the origins and evolution of these events, further improving their cosmological utility. Any future experiments in the rest-frame NIR will require knowledge of the SN Ia NIR spectroscopic diversity, which is currently based on a small sample of observed spectra. Along with the accompanying paper, Phillips et al., we introduce the Carnegie Supernova Project-II (CSP-II), to follow-up nearby SNe Ia in both the optical and the NIR. In particular, this paper focuses on the CSP-II NIR spectroscopy program, describing the survey strategy, instrumental setups, data reduction, sample characteristics, and future analyses on the data set. In collaboration with the Harvard-Smithsonian Center for Astrophysics (CfA) Supernova Group, we obtained 661 NIR spectra of 157 SNe Ia. Within this sample, 451 NIR spectra of 90 SNe Ia have corresponding CSP-II follow-up light curves. Such a sample will allow detailed studies of the NIR spectroscopic properties of SNe Ia, providing a different perspective on the properties of the unburned material; the radioactive and stable nickel produced; progenitor magnetic fields; and searches for possible signatures of companion stars.
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| 4. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Phillips, M. M., et al.
(författare)
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Carnegie Supernova Project-II : Extending the Near-infrared Hubble Diagram for Type Ia Supernovae to z ∼ 0.1
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a Cosmology sample of similar to 100 Type. Ia supernovae located in the smooth Hubble flow (0.03 less than or similar to z less than or similar to 0.10). Light curves were also obtained of a Physics sample composed of 90 nearby Type. Ia supernovae at z <= 0.04 selected for near-infrared spectroscopic timeseries observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.
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| 6. |
- Stritzinger, Maximilian, et al.
(författare)
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THE CARNEGIE SUPERNOVA PROJECT : SECOND PHOTOMETRY DATA RELEASE OF LOW-REDSHIFT TYPE Ia SUPERNOVAE
- 2011
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 142:5, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The Carnegie Supernova Project (CSP) was a five-year observational survey conducted at Las Campanas Observatory that obtained, among other things, high-quality light curves of similar to 100 low-redshift Type Ia supernovae (SNe Ia). Presented here is the second data release of nearby SN Ia photometry consisting of 50 objects, with a subset of 45 having near-infrared follow-up observations. Thirty-three objects have optical pre-maximum coverage with a subset of 15 beginning at least five days before maximum light. In the near-infrared, 27 objects have coverage beginning before the epoch of B-band maximum, with a subset of 13 beginning at least five days before maximum. In addition, we present results of a photometric calibration program to measure the CSP optical (uBgVri) bandpasses with an accuracy of similar to 1%. Finally, we report the discovery of a second SN Ia, SN 2006ot, similar in its characteristics to the peculiar SN 2006bt.
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| 7. |
- Benedict, G. Fritz, et al.
(författare)
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Distance scale zero points from galactic RR Lyrae star parallaxes
- 2011
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 142:6, s. 187-
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Tidskriftsartikel (refereegranskat)abstract
- We present new absolute trigonometric parallaxes and proper motions for seven Population II variable stars-five RR Lyr variables: RZ Cep, XZ Cyg, SU Dra, RR Lyr, and UV Oct; and two type 2 Cepheids: VY Pyx and kappa Pav. We obtained these results with astrometric data from Fine Guidance Sensors, white-light interferometers on Hubble Space Telescope. We find absolute parallaxes in milliseconds of arc: RZ Cep, 2.12 +/- 0.16 mas; XZ Cyg, 1.67 +/- 0.17 mas; SU Dra, 1.42 +/- 0.16 mas; RR Lyr, 3.77 +/- 0.13 mas; UV Oct, 1.71 +/- 0.10 mas; VY Pyx, 6.44 +/- 0.23 mas; and. Pav, 5.57 +/- 0.28 mas; an average sigma(pi)/pi = 5.4%. With these parallaxes, we compute absolute magnitudes in V and K bandpasses corrected for interstellar extinction and Lutz-Kelker-Hanson bias. Using these RR Lyrae variable star absolute magnitudes, we then derive zero points for M(V)-[Fe/H] and M(K)-[Fe/H]-log P relations. The technique of reduced parallaxes corroborates these results. We employ our new results to determine distances and ages of several Galactic globular clusters and the distance of the Large Magellanic Cloud. The latter is close to that previously derived from Classical Cepheids uncorrected for any metallicity effect, indicating that any such effect is small. We also discuss the somewhat puzzling results obtained for our two type 2 Cepheids.
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| 8. |
- Burns, Christopher R., et al.
(författare)
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THE CARNEGIE SUPERNOVA PROJECT : LIGHT-CURVE FITTING WITH SNooPy
- 2011
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 141:1, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- In providing an independent measure of the expansion history of the universe, the Carnegie Supernova Project (CSP) has observed 71 high-z Type Ia supernovae (SNe Ia) in the near-infrared bands Y and J. These can be used to construct rest-frame i-band light curves which, when compared to a low-z sample, yield distance moduli that are less sensitive to extinction and/or decline-rate corrections than in the optical. However, working with NIR observed and i-band rest-frame photometry presents unique challenges and has necessitated the development of a new set of observational tools in order to reduce and analyze both the low-z and high-z CSP sample. We present in this paper the methods used to generate uBVgriYJH light-curve templates based on a sample of 24 high-quality low-z CSP SNe. We also present two methods for determining the distances to the hosts of SN Ia events. A larger sample of 30 low-z SNe Ia in the Hubble flow is used to calibrate these methods. We then apply the method and derive distances to seven galaxies that are so nearby that their motions are not dominated by the Hubble flow.
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| 9. |
- Dhawan, Suhail, et al.
(författare)
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A Uniform Type Ia Supernova Distance Ladder with the Zwicky Transient Facility : Absolute Calibration Based on the Tip of the Red Giant Branch Method
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 934:2
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Tidskriftsartikel (refereegranskat)abstract
- The current Cepheid-calibrated distance ladder measurement of H0 is reported to be in tension with the values inferred from the cosmic microwave background (CMB), assuming standard cosmology. However, some tip of the red giant branch (TRGB) estimates report H0 in better agreement with the CMB. Hence, it is critical to reduce systematic uncertainties in local measurements to understand the Hubble tension. In this paper, we propose a uniform distance ladder between the second and third rungs, combining Type Ia supernovae (SNe Ia) observed by the Zwicky Transient Facility (ZTF) with a TRGB calibration of their absolute luminosity. A large, volume-limited sample of both calibrator and Hubble flow SNe Ia from the same survey minimizes two of the largest sources of systematics: host-galaxy bias and nonuniform photometric calibration. We present results from a pilot study using the existing TRGB distance to the host galaxy of ZTF SN Ia SN 2021rhu (aka ZTF21abiuvdk) in NGC7814. Combining the ZTF calibrator with a volume-limited sample from the first data release of ZTF Hubble flow SNe Ia, we infer H0 = 76.94 ± 6.4 km s−1 Mpc−1, an 8.3% measurement. The error budget is dominated by the single object calibrating the SN Ia luminosity in this pilot study. However, the ZTF sample includes already five other SNe Ia within ∼20 Mpc for which TRGB distances can be obtained with the Hubble Space Telescope. Finally, we present the prospects of building this distance ladder out to 80 Mpc with James Webb Space Telescope observations of more than 100 ZTF SNe Ia.
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| 10. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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