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- 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
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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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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- Subramanian, Arunprabaharan, et al.
(author)
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Trade-off between Zr Passivation and Sn Doping on Hematite Nanorod Photoanodes for Efficient Solar Water Oxidation : Effects of a ZrO2 Underlayer and FTO Deformation
- 2016
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 8:30, s. 19428-19437
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Journal article (peer-reviewed)abstract
- Herein we report the influence of a ZrO2 underlayer on the PEC (photoelectrochemical) behavior of hematite nanorod photoanodes for efficient solar water splitting. Particular attention was given to the cathodic shift in onset potential and photocurrent enhancement. Akaganite (beta-FeOOH) nanorods were grown on ZrO2-coated FTO (fluorine-doped tin oxide) substrates. Sintering at 800 degrees C transformed akaganite to the hematite (alpha-Fe2O3) phase and induced Sn diffusion into the crystal structure of hematite nanorods from the FTO substrates and surface migration, shallow doping of Zr atoms from the ZrO2 underlayer. The ZrO2 underlayer-treated photoanode showed better water oxidation performance compared to the pristine (alpha-Fe2O3) photoanode. A cathodic shift in the onset potential and photocurrent enhancement was achieved by surface passivation and shallow doping of Zr from the ZrO2 underlayer, along with Sn doping from the FTO substrate to the crystal lattice of hematite nanorods. The Zr based hematite nanorod photoanode achieved 1 mA/cm(2) at 1.23 V-RHE with a low turn-on voltage of 0.80 V-RHE. Sn doping and Zr passivation, as well as shallow doping, were confirmed by XPS, I-ph, and M-S plot analyses. Electrochemical impedance spectroscopy revealed that the presence of a ZrO2 underlayer decreased the deformation of FTO substrate, improved electron transfer at the hematite/FTO interface and increased charge-transfer resistance at the electrolyte/hematite interface. This is the first systematic investigation of the effects of Zr passivation, shallow doping, and Sn doping on hematite nanorod photoanodes through application of a ZrO2 underlayer on the FTO substrate.
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- Annamalai, Alagappan, et al.
(author)
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Sn/Be Sequentially co-doped Hematite Photoanodes for Enhanced Photoelectrochemical Water Oxidation : Effect of Be2+ as co-dopant
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- For ex-situ co-doping methods, sintering at high temperatures enables rapid diffusion of Sn4+ and Be2+ dopants into hematite (alpha-Fe2O3) lattices, without altering the nanorod morphology or damaging their crystallinity. Sn/Be co-doping results in a remarkable enhancement in photocurrent (1.7 mA/cm(2)) compared to pristine alpha-Fe2O3 (0.7 mA/cm(2)), and Sn4+ mono-doped alpha-Fe2O3 photoanodes (1.0 mA/cm(2)). From first-principles calculations, we found that Sn4+ doping induced a shallow donor level below the conduction band minimum, which does not contribute to increase electrical conductivity and photocurrent because of its localized nature. Additionally, Sn4+-doping induce local micro-strain and a decreased Fe-O bond ordering. When Be2+ was co-doped with Sn4+-doped alpha-Fe2O3 photoanodes, the conduction band recovered its original state, without localized impurities peaks, also a reduction in micro-strain and increased Fe-O bond ordering is observed. Also the sequence in which the ex-situ co-doping is carried out is very crucial, as Be/Sn co-doping sequence induces many under-coordinated O atoms resulting in a higher micro-strain and lower charge separation efficiency resulting undesired electron recombination. Here, we perform a detailed systematic characterization using XRD, FESEM, XPS and comprehensive electrochemical and photoelectrochemical studies, along with sophisticated synchrotron diffraction studies and extended X-ray absorption fine structure.
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