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- 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. |
- Berg, Alexis, et al.
(författare)
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Interannual Coupling between Summertime Surface Temperature and Precipitation over Land: Processes and Implications for Climate Change
- 2015
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Ingår i: Journal of Climate. - 1520-0442. ; 28:3, s. 1308-1328
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Tidskriftsartikel (refereegranskat)abstract
- Widespread negative correlations between summertime-mean temperatures and precipitation over land regions are a well-known feature of terrestrial climate. This behavior has generally been interpreted in the context of soil moisture atmosphere coupling, with soil moisture deficits associated with reduced rainfall leading to enhanced surface sensible heating and higher surface temperature. The present study revisits the genesis of these negative temperature precipitation correlations using simulations from the Global Land Atmosphere Coupling Experiment phase 5 of the Coupled Model Intercomparison Project (GLACE-CMIP5) multimodel experiment. The analyses are based on simulations with five climate models, which were integrated with prescribed (noninteractive) and with interactive soil moisture over the period 1950-2100. While the results presented here generally confirm the interpretation that negative correlations between seasonal temperature and precipitation arise through the direct control of soil moisture on surface heat flux partitioning, the presence of widespread negative correlations when soil moisture atmosphere interactions are artificially removed in at least two out of five models suggests that atmospheric processes, in addition to land surface processes, contribute to the observed negative temperature precipitation correlation. On longer time scales, the negative correlation between precipitation and temperature is shown to have implications for the projection of climate change impacts on near-surface climate: in all models, in the regions of strongest temperature precipitation anticorrelation on interannual time scales, long-term regional warming is modulated to a large extent by the regional response of precipitation to climate change, with precipitation increases (decreases) being associated with minimum (maximum) warming. This correspondence appears to arise largely as the result of soil moisture atmosphere interactions.
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