| 2. |
- 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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| 3. |
- Zhang, Wei-Wei, et al.
(författare)
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Thermodynamic Assessment of the Cu-B System Supported by Key Experiment and First-Principles Calculations
- 2009
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Ingår i: Journal of Phase Equilibria and Diffusion. - : Springer Science and Business Media LLC. - 1547-7037 .- 1863-7345. ; 30:5, s. 480-486
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Tidskriftsartikel (refereegranskat)abstract
- The Cu-B system was investigated via a hybrid approach of key experiment and thermodynamic modeling. Based on the critically assessed Cu-B phase diagram, seven crucial alloys were selected and prepared by arc melting the pure elements. An inductively coupled plasma-atomic emission spectrometric analysis was conducted to determine the compositions of the prepared alloys. The phase equilibria were determined by using x-ray diffraction, electron probe microanalysis, and differential thermal analysis. The temperature associated with the eutectic reaction, L double left right arrow (B) + (Cu); was measured to be 1028 +/- 2 degrees C. First-principles calculations indicate that the energy of inserting a B atom into the interstitial vacancy (Va) site of the lattice for Cu atoms is marginally lower than that of substituting for a Cu atom with a B atom. Consequently, the sublattice model (Cu)(B, Va) in which B atoms occupy the interstitial sites was employed for the fcc (Cu) phase rather than the model (Cu, B)(Va) in which B atoms substitute for Cu atoms. A thermodynamic modeling of the Cu-B system was then performed by considering the reliable literature data and the present experimental results. A good agreement between modeling and experiment was obtained.
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