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- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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- Duell, E. J., et al.
(författare)
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Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2164-2175
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Tidskriftsartikel (refereegranskat)abstract
- Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort. What's new Because the incidence of pancreatic cancer is 30-50% higher in men than women, researchers have wondered whether exposure to estrogen might offer a protective effect. The answer thus far has been unclear, however. In this study, the authors examined menstrual and reproductive factors in women, as well as exogenous hormone use. They also examined variants of the CYP17A1 gene in both women and men, as this gene is essential for sex-steroid metabolism. Only early age of menarche showed any association with pancreatic cancer risk. Copyright © 2012 UICC.
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- Buckland, G., et al.
(författare)
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Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:10, s. 2504-2511
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
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- Jenab, M, et al.
(författare)
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Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition
- 2006
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 95:3, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.
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- Kukkonen, J., et al.
(författare)
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Towards a Comprehensive Evaluation of the Environmental and Health Impacts of Shipping Emissions
- 2022
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Ingår i: Springer Proceedings in Complexity. - Cham : Springer International Publishing. - 2213-8684 .- 2213-8692. ; , s. 329-336
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Konferensbidrag (refereegranskat)abstract
- We present a new concept for marine research, applied in the EU-funded project EMERGE, “Evaluation, control and Mitigation of the EnviRonmental impacts of shippinG Emissions” (2020–2024; https://emerge-h2020.eu/ ). For the first time, both the various marine and atmospheric impacts of the shipping sector have been and will be comprehensively analyzed, using a concerted modelling and measurements framework. The experimental part of the project focuses on five European geographical case studies in different ecologically vulnerable regions, and a mobile onboard case study. The EMERGE consortium has also developed a harmonised and integrated modelling framework to assess the combined impacts of shipping emissions, both (i) on the marine ecosystems and (ii) the atmospheric environment. The first results include substantial refinements of a range of models to be applied, especially those for the STEAM and OpenDrift models. In particular, the STEAM (Ship Traffic Emission Assessment Model) model has been extended to allow for the effects of atmospheric and oceanographic factors on the fuel consumption and emissions of the ships. The OpenDrift model has been improved to take into account the partitioning, degradation, and volatilization of pollutants in water. The predicted emission and discharge values have been used as input for both regional scale atmospheric dispersion models, such as WRF-CMAQ (Weather Research and Forecasting—Community Multiscale Air Quality Model) and SILAM (System for Integrated modeLling of Atmospheric composition), and water quality and circulation models, such as OpenDrift (Open source model for the drifting of substances in the ocean) and Delft3D (oceanographic model). The case study regions are Eastern Mediterranean, Northern Adriatic Sea, the Lagoon of Aveiro, the Solent Strait and the Öresund Strait. We have also conducted a substantial part of the experimental campaigns scheduled in the project. The final assessment will include the benefits and costs of control and mitigation options affecting water quality, air pollution exposure, health impacts, climate forcing, and ecotoxicological effects and bioaccumulation of pollutants in marine biota.
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- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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