• Gallstones and incident colorectal cancer in a large pan-European cohort study.

      Ward, Heather A; Murphy, Neil; Weiderpass, Elisabete; Leitzmann, Michael F; Aglago, Elom; Gunter, Marc J; Freisling, Heinz; Jenab, Mazda; Boutron-Ruault, Marie-Christine; Severi, Gianluca; et al. (2018-12-26)
      Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.
    • Gap assessment in current soil monitoring networks across Europe for measuring soil functions

      van Leeuwen, J P; Saby, N P A; Jones, A; Louwagie, G; Micheli, E; Rutgers, M; Schulte, R P O; Spiegel, H; Toth, G; Creamer, R E (2017-12-01)
    • Gastro-intestinale klachten bij meningokokkeninfectie: Opkomst van serogroep W

      Wunderink, H F; Vlasveld, I N; Knol, M J; van der Ende, A; van Essen, E H R; Kuijper, E J (2017)
      Meningococcal disease usually presents as meningitis and/or septicaemia, but can also present as pneumonia or arthritis. Since 2000, a worldwide increase in meningococcal disease is reported which is caused by a new virulent clone of serogroup W (MenW:cc11). This subtype is more likely to give an atypical clinical presentation and results in high mortality rates.
    • Geen paniek! : Zelfredzaamheid bij uitbraken van infectieziekten

      Helsloot, I (RIVM, 2006-09-01)
      The understanding of citizen response to disaster is crucial to outbreak management of infectious diseases. Large scale outbreaks cannot be mitigated without the active corporation of citizens. This article shows that citizens in general will not panic, are not helpless and will not start plundering. Inappropriate actions and communication of authorities may cause unwanted reactions of citizen which then are labelled by both authorities and media as panic or irrational behaviour.
    • Gender and Educational Differences in the Association between Lifestyle and Cognitive Decline over 10 Years: The Doetinchem Cohort Study.

      Deckers, Kay; Nooyens, Astrid; van Boxtel, Martin; Verhey, Frans; Verschuren, Monique; Köhler, Sebastian (2018-11-28)
      Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear. The present study aims to clarify this by prospectively investigating the relationship between health- and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level. 2,347 cognitive healthy individuals (mean age = 54.8, SD = 6.8, range: 41-71; 51.8% female; 26.2% low education) from the Doetinchem Cohort Study were examined for cognitive function at baseline, and at 5- and 10-year follow-up. Health- and lifestyle factors were captured by a poly-environmental risk score labelled 'LIfestyle for BRAin Health' (LIBRA). This score consists of 12 modifiable risk and protective factors for cognitive decline and dementia, with higher scores indicating greater risk (range: -2.7 to +12.7). Heterogeneity in associations between LIBRA and decline in verbal memory, cognitive flexibility, and mental speed between males and females and individuals with different levels of education were assessed in linear mixed models. Overall, higher LIBRA scores predicted faster decline in verbal memory, cognitive flexibility, and mental speed over 10 years. Higher LIBRA scores were further associated with increased risk for incident cognitive impairment (one-point increase in LIBRA: HR = 1.09, 1.04-1.14, p = 0.001). In general, these effects were similar across gender and educational level.
    • Gender asymmetry in concurrent partnerships and HIV prevalence.

      Leung, Ka Yin; Powers, Kimberly A; Kretzschmar, Mirjam (2017)
      The structure of the sexual network of a population plays an essential role in the transmission of HIV. Concurrent partnerships, i.e. partnerships that overlap in time, are important in determining this network structure. Men and women may differ in their concurrent behavior, e.g. in the case of polygyny where women are monogamous while men may have concurrent partnerships. Polygyny has been shown empirically to be negatively associated with HIV prevalence, but the epidemiological impacts of other forms of gender-asymmetric concurrency have not been formally explored. Here we investigate how gender asymmetry in concurrency, including polygyny, can affect the disease dynamics. We use a model for a dynamic network where individuals may have concurrent partners. The maximum possible number of simultaneous partnerships can differ for men and women, e.g. in the case of polygyny. We control for mean partnership duration, mean lifetime number of partners, mean degree, and sexually active lifespan. We assess the effects of gender asymmetry in concurrency on two epidemic phase quantities (R0 and the contribution of the acute HIV stage to R0) and on the endemic HIV prevalence. We find that gender asymmetry in concurrent partnerships is associated with lower levels of all three epidemiological quantities, especially in the polygynous case. This effect on disease transmission can be attributed to changes in network structure, where increasing asymmetry leads to decreasing network connectivity.
    • Gender- and age-dependencies of oxidative stress, as detected based on the steady state concentrations of different biomarkers in the MARK-AGE study.

      Pinchuk, Ilya; Weber, Daniela; Kochlik, Bastian; Stuetz, Wolfgang; Toussaint, Olivier; Debacq-Chainiaux, Florence; Dollé, Martijn E T; Jansen, Eugène H J M; Gonos, Efstathios S; Sikora, Ewa; et al. (2019-06-01)
    • Gene profiling-based phenotyping for identification of cellular parameters that contribute to fitness, stress-tolerance and virulence of Listeria monocytogenes variants.

      Koomen, Jeroen; den Besten, Heidy M W; Metselaar, Karin I; Tempelaars, Marcel H; Wijnands, Lucas M; Zwietering, Marcel H; Abee, Tjakko (2018-06-07)
      Microbial population heterogeneity allows for a differential microbial response to environmental stresses and can lead to the selection of stress resistant variants. In this study, we have used two different stress resistant variants of Listeria monocytogenes LO28 with mutations in the rpsU gene encoding ribosomal protein S21, to elucidate features that can contribute to fitness, stress-tolerance and host interaction using a comparative gene profiling and phenotyping approach. Transcriptome analysis showed that 116 genes were upregulated and 114 genes were downregulated in both rpsU variants. Upregulated genes included a major contribution of SigB-controlled genes such as intracellular acid resistance-associated glutamate decarboxylase (GAD) (gad3), genes involved in compatible solute uptake (opuC), glycerol metabolism (glpF, glpK, glpD), and virulence (inlA, inlB). Downregulated genes in the two variants involved mainly genes involved in flagella synthesis and motility. Phenotyping results of the two rpsU variants matched the gene profiling data including enhanced freezing resistance conceivably linked to compatible solute accumulation, higher glycerol utilisation rates, and better adhesion to Caco 2 cells presumably linked to higher expression of internalins. Also, bright field and electron microscopy analysis confirmed reduced flagellation of the variants. The activation of SigB-mediated stress defence offers an explanation for the multiple-stress resistant phenotype in rpsU variants.
    • Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations.

      Jannasch, Franziska; Kröger, Janine; Agnoli, Claudia; Barricarte, Aurelio; Boeing, Heiner; Cayssials, Valerie; Colorado-Yohar, Sandra; Dahm, Christina C; Dow, Courtney; Fagherazzi, Guy; et al. (2019-06-01)
    • Genes for the majority of group a streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease.

      McMillan, David J; Beiko, R G; Geffers, R; Buer, Jan; Schouls, Leo M; Vlaminckx, B J M; Wannet, Wim J B; Sriprakash, K S; Chhatwal, G S (2006-10-01)
      BACKGROUND: The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. METHODS: In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. RESULTS: Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. CONCLUSIONS: Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/or host factors.
    • Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

      Campa, Daniele; Matarazzi, Martina; Greenhalf, William; Bijlsma, Maarten; Saum, Kai-Uwe; Pasquali, Claudio; van Laarhoven, Hanneke; Szentesi, Andrea; Federici, Francesca; Vodicka, Pavel; et al. (2018-10-16)
      Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.
    • The genetic diversity of Borrelia afzelii is not maintained by the diversity of the rodent hosts.

      Coipan, Claudia E; van Duijvendijk, Gilian L A; Hofmeester, Tim R; Takumi, Katsuhisa; Sprong, Hein (2018-08-06)
      Small mammals are essential in the enzootic cycle of many tick-borne pathogens (TBP). To understand their contribution to the genetic diversity of Borrelia afzelii, the most prevalent TBP in questing Ixodes ricinus, we compared the genetic variants of B. afzelii at three distinct genetic loci. We chose two plasmid loci, dbpA and ospC, and a chromosomal one, IGS.
    • Genetic risk scores do not improve asthma prediction in childhood.

      Dijk, F Nicole; Folkersma, Charlotte; Gruzieva, Olena; Kumar, Ashish; Wijga, Alet H; Gehring, Ulrike; Kull, Inger; Postma, Dirkje S; Vonk, Judith M; Melén, Erik; et al. (2019-05-27)
    • Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

      Machiela, Mitchell J; Hofmann, Jonathan N; Carreras-Torres, Robert; Brown, Kevin M; Johansson, Mattias; Wang, Zhaoming; Foll, Matthieu; Li, Peng; Rothman, Nathaniel; Savage, Sharon A; et al. (2017-11)
      Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.
    • Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

      Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; et al. (2017-05)
      Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
    • Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands

      Cremer, Jeroen; Hofstraat, Sanne H. I.; van Heiningen, Francoise; Veldhuijzen, Irene K.; van Benthem, Birgit H. B.; Benschop, Kimberley S. M.; Laboratory for Infectious Diseases and Screening, Center for Infectious Disease Control; National Institute for Public Health and the Environment; Bilthoven The Netherlands; Laboratory for Infectious Diseases and Screening, Center for Infectious Disease Control; National Institute for Public Health and the Environment; Bilthoven The Netherlands; Laboratory for Infectious Diseases and Screening, Center for Infectious Disease Control; National Institute for Public Health and the Environment; Bilthoven The Netherlands; Laboratory for Infectious Diseases and Screening, Center for Infectious Disease Control; National Institute for Public Health and the Environment; Bilthoven The Netherlands; et al. (2018-10)
    • Genome Detective: An Automated System for Virus Identification from High-throughput sequencing data.

      Vilsker, Michael; Moosa, Yumna; Nooij, Sam; Fonseca, Vagner; Ghysens, Yoika; Dumon, Korneel; Pauwels, Raf; Alcantara, Luiz Carlos; Vanden Eynden, Ewout; Vandamme, Anne-Mieke; et al. (2018-08-16)
      Genome Detective is an easy to use web-based software application that assembles the genomes of viruses quickly and accurately. The application uses a novel alignment method that constructs genomes by reference-based linking of de-novo contigs by combining amino-acids and nucleotide scores. The software was optimized using synthetic datasets to represent the great diversity of virus genomes. The application was then validated with next generation sequencing data of hundreds of viruses. User time is minimal and it is limited to the time required to upload the data.
    • Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.

      Pasanen, Anu; Karjalainen, Minna K; Bont, Louis; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie; Nuolivirta, Kirsi; Jartti, Tuomas; et al. (2017-01-31)
      Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish-Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10-5) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size.