A H Zwinderman

Netherlands Bioinformatics Centre, Nymegen, Gelderland, Netherlands

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Publications (750)3590.24 Total impact

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    ABSTRACT: 2. The history of diagnosing Marfan syndrome 3. The FBN1 gene 4. Overview of literature 5. Different types of FBN1 mutations 6. Conclusion 7. Expert opinion Introduction: Marfan syndrome (MFS) is a connective tissue disorder with highly variable features in cardiovascular, ocular and skeletal systems. MFS is generally caused by one of the 2900-plus described different genetic mutations in the fibrillin-1 gene (FBN1). Areas covered: By revising the Ghent criteria in 2010, more weight has been given to genetic testing in the diagnosis of MFS. We provide an overview of correlations between different mutation types and clinical MFS features by using the Universal Mutation Database (UMD). Expert opinion: In this paper, we classified FBN1 mutations based on their action on DNA level and we found the following genotype--phenotype corre-lations: i) cysteine mutations are associated with ectopia lentis; ii) introduc-tion of a cysteine leads to less severe involvement of cardiovascular and skeletal system; iii) whole gene deletions and premature termination codon (PTC) mutations are associated with increased skeletal and cardiovascular involvement, but lower prevalence of ectopia lentis and iv) intronic mutations lead to MFS by exon skipping, small insertions/deletions and PTC mutations. Classification based on mutation effect at protein level (reduced vs truncated/deformed fibrillin-1) may partly explain genotype--phenotype asso-ciation and warrants further investigation for individualized prognosis and treatment.
    Expert Opinion on Orphan Drugs. 08/2014; 2(10).
  • N van Geloven, R B Geskus, B W Mol, A H Zwinderman
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    ABSTRACT: When estimating the probability of natural conception from observational data on couples with an unfulfilled child wish, the start of assisted reproductive therapy (ART) is a competing event that cannot be assumed to be independent of natural conception. In clinical practice, interest lies in the probability of natural conception in the absence of ART, as this probability determines the need for therapy. We thus want to estimate the marginal cumulative pregnancy distribution. Without assumptions on the dependence structure between the two competing events, this marginal distribution is not identifiable. We first use inverse probability of censoring weighting assuming that the factors influencing the choice to start ART are known. Then, we parameterize the event distributions for conception and for start of ART and use copulas to account for the dependency between both events. By using these two ways of correcting for the dependent risk of treatment, we obtain a plausible estimation region for the cumulative pregnancy curve and for the prognostic effect of tubal tests. Copyright © 2014 John Wiley & Sons, Ltd.
    Statistics in medicine. 08/2014;
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    ABSTRACT: To investigate how the summary estimates in diagnostic test accuracy (DTA) systematic reviews are affected when searches are limited to MEDLINE.
    Journal of clinical epidemiology. 07/2014;
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    ABSTRACT: Carotid intima-media thickness (CIMT) is a marker for atherosclerosis. Adult post-coarctectomy patients (CoA) demonstrate an increased cardiovascular risk and increased CIMT compared to controls. This study evaluates the effect of high dose statins on the change in CIMT and cardiovascular risk.
    International journal of cardiology. 06/2014;
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    ABSTRACT: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Increasing age has been associated with elevated circulating levels of pro-inflammatory mediators. We aimed to determine the impact of aging on the systemic inflammatory response to CAP. In total 201 CAP patients were enrolled. Blood samples were obtained upon presentation, and day 2, 3, 5. For the current analysis patients ≤ 50 and ≥ 80 years were included. Pneumonia Severity Index (PSI) score was calculated at presentation. The study encompassed 46 CAP patients ≤ 50 years (median 37 years) and 41 CAP patients ≥ 80 years (median 84 years). In both groups Streptococcus pneumoniae was the common causative microorganism. Whereas most young patients had a PSI score of I (54%), 98% of old patients had a PSI score ≥ III (p < 0.001). Four elderly patients died versus none of the young patients (p = 0.045). Old patients demonstrated lower serum C-reactive protein levels on admission and during the course of their hospitalization (p = 0.001) in spite of more severe disease. Serum concentrations of pro-inflammatory (interleukin (IL)-6 and IL-8) and anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) did not differ between age groups, although admission IL-8 levels tended to be higher in old patients (p = 0.05). Cytokine levels positively correlated with PSI in young but not in old patients. These results suggest that elderly patients show an absolute (C-reactive protein) or relative (cytokines) reduction in their systemic inflammatory response on admission for CAP.
    Clinical Microbiology and Infection 06/2014; · 4.58 Impact Factor
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    ABSTRACT: Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10(-4)). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples. Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an 'extreme genetics' approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may, therefore, not lead to significant gains in statistical power.European Journal of Human Genetics advance online publication, 11 June 2014; doi:10.1038/ejhg.2014.101.
    European journal of human genetics: EJHG 06/2014; · 3.56 Impact Factor
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    ABSTRACT: The aim of this study is to explore DNA hypermethylation analysis in sputum and exhaled breath analysis for their complementary, non-invasive diagnostic capacity in lung cancer.
    Journal of clinical pathology. 06/2014; 67(8):707-711.
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    ABSTRACT: -The pathogenic phospholamban (PLN) R14del mutation causes dilated and/or arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of PLN R14del mutation carriers.
    Circulation Cardiovascular Genetics 06/2014; · 6.73 Impact Factor
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    ABSTRACT: Asthma and atopy share common characteristics including type 2 helper T-cell mediated inflammation. However, only asthma is associated with variable airways obstruction. The complex cellular and molecular pathways distinguishing asthma and atopy can now be captured by transcriptomic analysis (RNA-Seq). We hypothesized that the transcriptomic profile of airway smooth muscle (ASM) distinguishes atopic asthma from atopic healthy controls. First, we compared the ASM transcriptomic profiles of endobronchial biopsies between glucocorticoid-free, atopic asthma patients, and atopic and non-atopic healthy controls. Second, we investigated the association between ASM transcriptomic profiles and airway function.
    Allergy 05/2014; · 5.88 Impact Factor
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    ABSTRACT: To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance. Cross-sectional evaluation comparing two methods (Bland-Altman). Tertiary care outpatients. Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation. Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods. Twenty-two patients (mean age 33 ± 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries). Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation. There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle.
    Congenital Heart Disease 04/2014; · 1.01 Impact Factor
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    ABSTRACT: There is a need for biological markers of the acute respiratory distress syndrome (ARDS). Exhaled breath contains hundreds of metabolites in the gas phase, some of which reflect (patho)physiological processes. We aimed to determine the diagnostic accuracy of metabolites in exhaled breath as biomarkers of ARDS.Breath from ventilated intensive care unit patients (n = 101) was analysed using gas chromatography and mass spectrometry during the first day of admission. ARDS was defined by the Berlin definition. Training and temporal validation cohorts were used.23 patients in the training cohort (n = 53) had ARDS. Three breath metabolites, octane, acetaldehyde and 3-methylheptane, could discriminate between ARDS and controls with an area under the receiver operating characteristic curve (AUC) of 0.80. Temporal external validation (19 ARDS cases in a cohort of 48) resulted in an AUC of 0.78. Discrimination was insensitive to adjustment for severity of disease, a direct or indirect cause of ARDS, comorbidities, or ventilator settings. Combination with the lung injury prediction score increased the AUC to 0.91 and improved net reclassification by 1.17.Exhaled breath analysis showed good diagnostic accuracy for ARDS, which was externally validated. These data suggest that exhaled breath analysis could be used for the diagnostic assessment of ARDS.
    European Respiratory Journal 04/2014; · 6.36 Impact Factor
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    ABSTRACT: Doel Onderzoeken in hoeverre patiëntgegevens en huisartskenmerken de zorgkosten verklaren van patiënten die hun huisarts frequent bezoeken gedurende 1-3 jaar. Opzet Observationeel onderzoek. Methode Er werd gebruikgemaakt van huisartsregistratiebestanden en declaratiegegevens van een zorgverzekeraar. Gepseudonimiseerde gegevens uit de dossiers van 16.531 patiënten (39 huisartsen) werden gekoppeld aan eerste- en tweedelijns kosten vergoed door een zorgverzekeraar in de periode 2007-2009. Huisartskenmerken werden verzameld via administratieve gegevens en een vragenlijst. Via multilevel lineaire regressieanalyse schatten we het effect van de duur van het frequente bezoek op de zorgkosten, na correctie voor aandoeningen van de patiënt en huisartskenmerken. Resultaten De ongecorrigeerde gemiddelde uitgaven in 3 jaar waren voor niet-frequente bezoekers €5.044 en voor frequente bezoekers €15.824. Na correctie voor bekende confounders bleven de zorgkosten voor frequente bezoekers aanzienlijk hoger. Hoe langer het frequente bezoek bestond, hoe hoger de kosten waren. Vergeleken met niet-frequente bezoekers waren de gecorrigeerde kosten voor 3 jaar zorg €1723 hoger voor patiënten die gedurende 1 jaar frequente bezoeker waren, en €5293 hoger voor patiënten die 3 jaar lang frequent bezoeker waren. Conclusie Frequente bezoekers van de huisarts genereren hoge zorgkosten, zowel in de eerste als in de tweede lijn. Deze kosten kunnen deels worden verklaard door de aandoeningen van patiënten en door kenmerken en werkstijl van de huisarts. Mogelijk spelen aandoeningen die nu niet door de huisarts worden geregistreerd, een rol. De mechanismen die deze extra uitgaven veroorzaken vereisen nader onderzoek.
    Nederlands tijdschrift voor geneeskunde 03/2014; 2014;158: A7117(158):A7117.
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    ABSTRACT: Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
    The American Journal of Human Genetics 02/2014; · 11.20 Impact Factor
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    ABSTRACT: To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of the polymorphism were compared between patients and controls. Associations between the LL, SL, and SS genotypes and fold increase of mean IELT were investigated. Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment with an ejaculation delay, whereas 11 patients (20.4%) did not respond; 44%, 18%, and 18% of the patients showed a fold increase in mean IELT of 2-10, 10-20, and more than 20, respectively. Of the 54 men, 14 (25.9%) had the LL genotype, 29 (53.7%) had the SL genotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of variance of the natural logarithm of fold increase in the IELT showed no statistically significant difference according to genotype (p=0.83). The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetine treatment-induced ejaculation delay in men with LPE.
    Korean journal of urology 02/2014; 55(2):129-33.
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    ABSTRACT: Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that: a) upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and b) that this is modulated by the presence of asthma and allergic rhinitis.Objectives: Identification of dsRNA-induced gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. This study had a cross-sectional design including 18 subjects: 6 patients with allergic asthma with concomitant rhinitis, 6 patients with allergic rhinitis, and 6 healthy controls. Comparing 6 subjects per group, the estimated false discovery rate was approximately 5%. RNA was extracted from isolated and cultured primary epithelial cells from nasal biopsies and bronchial brushings stimulated with dsRNA (poly(I:C)), and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and the Bioconductor Limma package. Overrepresentation of gene ontology groups were captured by GeneSpring GX12. In total, 17 subjects completed the study successfully (6 allergic asthma with rhinitis, 5 allergic rhinitis, 6 healthy controls). dsRNA-stimulated upper and lower airway epithelium from asthma patients demonstrated significantly fewer induced genes, exhibiting reduced down-regulation of mitochondrial genes. The majority of genes related to viral responses appeared to be similarly induced in upper and lower airways in all groups. However, the induction of several interferon-related genes (IRF3, IFNAR1, IFNB1, IFNGR1, IL28B) was impaired in patients with asthma. dsRNA differentially changes transcriptional profiles of primary nasal and bronchial epithelial cells from patients with allergic rhinitis with or without asthma and controls. Our data suggest that respiratory viruses affect mitochondrial genes, and we identified disease-specific genes that provide potential targets for drug development.
    Respiratory research 01/2014; 15(1):9. · 3.64 Impact Factor
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    ABSTRACT: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT1A receptor hyperfunction and 5-HT2C hypofunction. To investigate the relationship between 5-HT1A receptor gene (HTR1A)-C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is known to increase 5-HT1A receptor expression. A prospective study was conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for HTR1A gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR1A polymorphism were determined. Association between CC, CG, and GG genotypes and the IELT in men with LPE were investigated. IELT measured by stopwatch, HTR1A polymorphism. In this cohort of men with LPE, the geometric mean IELT was 23.8s. Of the 54 men, the CC, CG and GG genotype frequency for the C(1019)G polymorphism of the 5-HT1A gene was 33%, 43% and 24%, respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5, 27.7 and 36.0s, respectively (p=0.019). Compared to GG and CG genotypes, men with CC genotype had a 250% and 190% shorter ejaculation time, respectively. HTR1A gene polymorphism is associated with the IELT in men with LPE. Men with CC genotype have shorter IELTs than men with GG and CG genotypes.
    Pharmacology Biochemistry and Behavior 01/2014; · 2.61 Impact Factor
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    ABSTRACT: To determine the effect of losartan on aortic dilatation rate in adults with Marfan syndrome. Randomised, controlled multicentre clinical trial. Adult Marfan patients from the 4 Marfan centres in the Netherlands with a maximum of 1 aortic prosthesis were randomised to 100 mg losartan once daily or no additional losartan treatment. All patients continued their standard treatment, which consisted mainly of β-blockers. The primary outcome measure was a reduction in aortic dilatation rate. The secondary outcome measures were an increase in aortic volume and the incidence of the combined outcome measure: cardiovascular mortality, aortic dissection and aorta surgery. This trial was registered with the Dutch Trial Register (NTR1423). 233 patients were included. Absolute aortic diameters were measured at the beginning and at the end of the study. The aortic root dilatation rate after 3 years was significantly lower in patients in the losartan group than in those in the control group (0.77 mm/3 years (SD: 1.36) vs. 1.35 mm/3 years (SD: 1.55); p = 0.014). The dilatation rate in the trajectory beyond the aortic root was comparable in the two groups. There were no differences in the secondary outcome measures between the two groups. A subanalysis of patients with aortic root replacement surgery prior to inclusion in the study demonstrated that in this group losartan treatment led to a significant decrease in aortic arch dilatation rate versus standard treatment (0.50 mm/3 years (SD: 1.26) vs. 1.01 mm/3 years (1.31); p = 0.033). In adult Marfan patients, losartan treatment reduces the aortic root dilatation rate. After aortic root surgery, losartan treatment reduces dilatation rate of the aortic arch.
    Nederlands tijdschrift voor geneeskunde 01/2014; 158(2):A6845.
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    ABSTRACT: To analyze a recently published meta-analysis of six studies on 5-HTTLPR polymorphism and lifelong premature ejaculation (PE). Calculation of fraction observed and expected genotype frequencies and Hardy Weinberg equilibrium (HWE) of cases and controls. LL,SL and SS genotype frequencies of patients were subtracted from genotype frequencies of an ideal population (LL25%, SL50%, SS25%, p = 1 for HWE). Analysis of PCRs of six studies and re-analysis of the analysis and Odds ratios (ORs) reported in the recently published meta-analysis. Three studies deviated from HWE in patients and one study deviated from HWE in controls. In three studies in-HWE the mean deviation of genotype frequencies from a theoretical population not-deviating from HWE was small: LL(1.7%), SL(-2.3%), SS(0.6%). In three studies not-in-HWE the mean deviation of genotype frequencies was high: LL(-3.3%), SL(-18.5%) and SS(21.8%) with very low percentage SL genotype concurrent with very high percentage SS genotype. The most serious PCR deviations were reported in the three not-in-HWE studies. The three in-HWE studies had normal OR. In contrast, the three not-in-HWE studies had a low OR. In three studies not-in-HWE and with very low OR, inadequate PCR analysis and/or inadequate interpretation of its gel electrophoresis resulted in very low SL and a resulting shift to very high SS genotype frequency outcome. Consequently, PCRs of these three studies are not reliable. Failure to note the inadequacy of PCR tests makes such PCRs a confounding factor in clinical interpretation of genetic studies. Currently, a meta-analysis can only be performed on three studies-in-HWE. However, based on the three studies-in-HWE with OR of about 1 there is not any indication that in men with lifelong PE the frequency of LL,SL and SS genotype deviates from the general male population and/or that the SL or SS genotype is in any way associated with lifelong PE.
    PLoS ONE 01/2014; 9(3):e88031. · 3.53 Impact Factor
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    ABSTRACT: Obesity and type 2 diabetes (T2D) are highly prevalent among African migrants compared with European descent populations. The underlying reasons still remain a puzzle. Gene-environmental interaction is now seen as a potential plausible factor contributing to the high prevalence of obesity and T2D, but has not yet been investigated. The overall aim of the Research on Obesity and Diabetes among African Migrants (RODAM) project is to understand the reasons for the high prevalence of obesity and T2D among sub-Saharan Africans in diaspora by (1) studying the complex interplay between environment (eg, lifestyle), healthcare, biochemical and (epi)genetic factors, and their relative contributions to the high prevalence of obesity and T2D; (2) to identify specific risk factors within these broad categories to guide intervention programmes and (3) to provide a basic knowledge for improving diagnosis and treatment. RODAM is a multicentre cross-sectional study among homogenous sub-Saharan African participants (ie, Ghanaians) aged >25 years living in rural and urban Ghana, the Netherlands, Germany and the UK (http://rod-am.eu/). Standardised data on the main outcomes, genetic and non-genetic factors are collected in all locations. The aim is to recruit 6250 individuals comprising five subgroups of 1250 individuals from each site. In Ghana, Kumasi and Obuasi (urban stratum) and villages in the Ashanti region (rural stratum) are served as recruitment sites. In Europe, Ghanaian migrants are selected through the municipality or Ghanaian organisations registers. Ethical approval has been obtained in all sites. This paper gives an overview of the rationale, conceptual framework and methods of the study. The differences across locations will allow us to gain insight into genetic and non-genetic factors contributing to the occurrence of obesity and T2D and will inform targeted intervention and prevention programmes, and provide the basis for improving diagnosis and treatment in these populations and beyond.
    BMJ Open 01/2014; 4(3):e004877. · 1.58 Impact Factor
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    ABSTRACT: Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with pneumococcal meningitis. Pneumococci harboring these genes show increased growth in human blood and cerebrospinal fluid (CSF). Mouse models of meningitis and pneumonia showed that pneumococcal strains without arginine biosynthesis genes were attenuated in growth or cleared, from lung, blood and CSF. Thus, S. pneumoniae arginine synthesis genes promote growth and virulence in invasive pneumococcal disease.
    The Journal of Infectious Diseases 12/2013; · 5.85 Impact Factor

Publication Stats

18k Citations
3,590.24 Total Impact Points

Institutions

  • 2006–2014
    • Netherlands Bioinformatics Centre
      Nymegen, Gelderland, Netherlands
  • 2003–2014
    • University of Amsterdam
      • • Department of Clinical Epidemiology and Biostatistics
      • • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
    • Reinier de Graaf Groep
      Delft, South Holland, Netherlands
  • 1994–2014
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Academic Medical Center
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Vascular Medicine
      • • Department of Radiology
      • • Department of Cardiology and Cardio-thoracic Surgery
      • • Department of Neurology
      Amsterdamo, North Holland, Netherlands
  • 1992–2012
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 1990–2012
    • St. Antonius Ziekenhuis
      • • Department of Cardiology
      • • Department of Nuclear Medicine
      Nieuwegein, Provincie Utrecht, Netherlands
    • Leiden University Medical Centre
      • • Department of Cardiology
      • • Department of Radiology
      • • Department of Neurology
      • • Department of Nephrology
      • • Department of Rheumatology
      Leiden, South Holland, Netherlands
  • 2011
    • Ludwig-Maximilian-University of Munich
      • Department of Neurology
      München, Bavaria, Germany
  • 2010
    • Sint Franciscus Gasthuis Rotterdam
      Rotterdam, South Holland, Netherlands
    • Maasstad Ziekenhuis
      Rotterdam, South Holland, Netherlands
  • 2000–2010
    • Albert Schweitzer Ziekenhuis
      Dordt, South Holland, Netherlands
  • 1998–2009
    • Universiteit Utrecht
      • • Department of Pharmaceutical Sciences
      • • Division of Pharmacology and Pathofysiology
      • • Department of Medical Oncology
      Utrecht, Provincie Utrecht, Netherlands
  • 2008
    • HagaZiekenhuis van Den Haag
      's-Gravenhage, South Holland, Netherlands
  • 2005–2008
    • Collège de France
      Lutetia Parisorum, Île-de-France, France
  • 1990–2005
    • Leiden University
      • Leiden Amsterdam Center for Drug Research
      Leyden, South Holland, Netherlands
  • 2004
    • Medisch Centrum Leeuwarden
      Leewarden, Friesland, Netherlands
    • Universiteit Twente
      Enschede, Overijssel, Netherlands
  • 2002
    • Medisch Spectrum Twente
      • Rheumatology Department
      Enschede, Overijssel, Netherlands
  • 2001
    • University of British Columbia - Vancouver
      • Centre for Molecular Medicine and Therapeutics
      Vancouver, British Columbia, Canada
  • 1999–2001
    • Centraal Bureau voor de Statistiek
      's-Gravenhage, South Holland, Netherlands
  • 1995–2000
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 1997–1998
    • Martini Ziekenhuis
      Groningen, Groningen, Netherlands
    • Erasmus Universiteit Rotterdam
      • Department of Clinical Chemistry
      Rotterdam, South Holland, Netherlands
  • 1996
    • University of Groningen
      • Department of Cardiology
      Groningen, Province of Groningen, Netherlands
  • 1993
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
    • Catharina Ziekenhuis
      • Department of Radiology
      Eindhoven, North Brabant, Netherlands
  • 1991
    • Diakonessenhuis Utrecht
      Utrecht, Utrecht, Netherlands