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- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 2. |
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| 3. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Rodhe, Lena, et al.
(författare)
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Ammonia emissions after application of human urine to a clay soil for barley growth
- 2004
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Ingår i: Nutrient Cycling in Agroecosystems. - 1385-1314 .- 1573-0867. ; 68:2, s. 191-198
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Tidskriftsartikel (refereegranskat)abstract
- Important amounts of plant nutrients excreted by humans are found in human urine. This provides the motivation for separating urine and recycling it, as fertiliser, back to agricultural land for food or fodder production. There are some housing estates in Sweden, both blocks of flats and separate houses, in which urine-separating toilets have been installed. The urine is stored in covered basins and spread on agricultural land. The objective of the present study was to evaluate the influence of application rate, application techniques and time on NH3 emissions after application of source-separated human urine. Human urine was spread at different application rates (10, 20 and 60 Mg ha-1) before sowing (year 1 to 3) and when the barley crop was 20-30 cm high (year 2). Urine was spread with a plot spreader using two band-application techniques (with bands 0.25 m apart): trailing hoses and trailing shoes. In spring, band-spread urine with trailing hoses was incorporated with a harrow four hours after application. The four (year 1 and 3) or six (year 2) treatments were organised into a randomised block design with three replicates. An equilibrium concentration method was used for measuring ammonia emissions directly after application. After spring application with trailing hoses and harrowing after four hours, the nitrogen [N] loss as ammonia [NH3], average over 3 years, was 5% of the applied N, irrespective of the application rate. The largest loss (10% of the applied N) was measured after application of 60 t of urine per hectare in spring. Hardly any NH 3 loss occurred after incorporation with a harrow, with the exception of the highest application rate. Loss of NH3 was very low, close to 1% of the applied N, when the urine was incorporated directly into the soil in spring by band application with trailing shoes. Virtually no emissions were detected when the urine was applied to the growing crop, neither by trailing hoses nor by trailing shoes. This study shows that it is possible to apply human urine on bare soil or in growing barley crop with very low losses of N as NH3. Together with careful handling and the use of covered storage, nutrients in human urine could be recycled from households to agricultural land with low NH3 emissions.
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