Jj Houwing

Jj Houwing
Leiden University Medical Centre | LUMC · Department of Medical Statistics and Bioinformatics

PhD

About

382
Publications
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12,282
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Publications

Publications (382)
Article
Full-text available
Advancement of gene expression measurements in longitudinal studies enables the identification of genes associated with disease severity over time. However, problems arise when the technology used to measure gene expression differs between time points. Observed differences between the results obtained at different time points can be caused by techn...
Preprint
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Background: Nowadays, multiple omics data are measured on the same samples in the belief that these different omics datasets represent various aspects of the underlying biological systems. Integrating these omics datasets will facilitate the understanding of the systems. For this purpose, various methods have been proposed, such as Partial Least Sq...
Article
Full-text available
Background: Soil-transmitted helminths have been shown to have the immune regulatory capacity, which they use to enhance their long term survival within their host. As these parasites reside in the gastrointestinal tract, they might modulate the immune system through altering the gut bacterial composition. Although the relationships between helmint...
Article
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Purpose: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to...
Article
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Marginal tests based on individual SNPs are routinely used in genetic association studies. Studies have shown that haplotype‐based methods may provide more power in disease mapping than methods based on single markers when, for example, multiple disease‐susceptibility variants occur within the same gene. A limitation of haplotype‐based methods is t...
Article
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Background With the exponential growth in available biomedical data, there is a need for data integration methods that can extract information about relationships between the data sets. However, these data sets might have very different characteristics. For interpretable results, data-specific variation needs to be quantified. For this task, Two-wa...
Data
Relationship between indices of social anxiety and gray matter characteristics, corrected for level of depressive symptoms (sensitivity analysis 2)
Data
Detailed statistics of effects of social anxiety on, and heritability estimates of parameters of interest: general imaging phenotypes (tab 1); subcortical volumes (tab 2); cortical thickness (tab 3); cortical surface area (tab 4).
Data
Detailed statistics of effects of social anxiety on parameters of interest in sample without comorbidity (sensitivity analysis 1): subcortical volumes (tab 1); cortical thickness (tab 2); cortical surface area (tab 3).
Data
Relationship between indices of social anxiety and gray matter characteristics in selection of LFLSAD sample: participants with (comorbid) psychopathology other than (sub)clinical SAD were excluded (sensitivity analysis 1)
Data
Detailed statistics of effects of social anxiety on parameters of interest, corrected for level of depressive symptoms (sensitivity analysis 2): subcortical volumes (tab 1); cortical thickness (tab 2); cortical surface area (tab 3).
Data
Detailed statistics of effects of social anxiety on, and heritability estimates of non-ROIs: subcortical volumes (tab 1); cortical thickness (tab 2); cortical surface area (tab 3).
Article
Full-text available
Abstract The main goal of this paper is to estimate the effect of triglyceride levels on methylation of cytosine-phosphate-guanine (CpG) sites in multiple-case families. These families are selected because they have 2 or more cases of metabolic syndrome (primary phenotype). The methylations at the CpG sites are the secondary phenotypes. Ascertainme...
Data
The characteristics of participants of current study and total population in Nangapanda. (DOCX)
Data
Bacterial diversity in relation with helminth at pre and post-treatment. The Shannon (top) and richness (bottom) indices were computed in helminth infected (Helminth (+)) and uninfected (Helminth (-)) subjects. (TIF)
Data
List of primers and probe sequences used in detecting the helminth species. (DOCX)
Article
Full-text available
Members of longevous families live longer than individuals from similar birth cohorts and delay/escape age related diseases. Insight into this familial component of longevity can provide important knowledge about mechanisms protecting against age-related diseases. This familial component of longevity was studied in the Leiden Longevity Study which...
Chapter
Enrichment of predictive models with new biomolecular markers is an important task in high-dimensional omic applications. Increasingly, clinical studies include several sets of such omics markers available for each patient, measuring different levels of biological variation. As a result, one of the main challenges in predictive research is the inte...
Article
Full-text available
Very few molecular genetic studies of personality traits have used longitudinal phenotypic data, therefore molecular basis for developmental change and stability of personality remains to be explored. We examined the role of the monoamine oxidase A gene (MAOA) on extraversion and neuroticism from adolescence to adulthood, using modern latent variab...
Article
Full-text available
This study indicates that glycosylation of immunoglobulin G, the most abundant antibody in human blood, may convey useful information with regard to inflammation and metabolic health. IgG occurs in the form of different subclasses, of which the effector functions show significant variation. Our method provides subclass-specific IgG glycosylation pr...
Article
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With a rapid increase in volume and complexity of data sets there is a need for methods that can extract useful information in these data sets. Dimension reduction approaches such as Partial least squares (PLS) are increasingly being utilized for finding relationships between two data sets. However these methods often lack a probabilistic formulati...
Article
Background: Emerging evidence suggests that helminth infections are associated with lower insulin resistance (IR). Current deworming programmes might remove this helminth-associated protective effect. Therefore, we evaluated the anthelmintic treatment effect on changes in IR. Methods: We conducted a double-blind household-cluster-randomized plac...
Article
Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programs are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed t...
Article
31 Very few molecular genetic studies of personality traits have used longitudinal phenotypic 32 data, therefore molecular basis for developmental change and stability of personality remains 33 to be explored. We examined the role of the monoamine oxidase A gene (MAOA) on 34 extraversion and neuroticism from adolescence to adulthood, using modern l...
Article
Full-text available
Glycosylation is an abundant co- and post-translational protein modification of importance to protein processing and activity. While not template-defined, glycosylation does reflect the biological state of an organism and is a high-potential biomarker for disease and patient stratification. However, to interpret a complex but informative sample lik...
Article
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The case-control design is often used to test associations between the case-control status and genetic variants. In addition to this primary phenotype a number of additional traits, known as secondary phenotypes, are routinely recorded and typically associations between genetic factors and these secondary traits are studied too. Analysing secondary...
Article
Full-text available
Background In older people, chronological age may not be the best predictor of residual lifespan and mortality, because with age the heterogeneity in health is increasing. Biomarkers for biological age and residual lifespan are being developed to predict disease and mortality better at an individual level than chronological age. In the current pape...
Article
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For a better understanding of the biological mechanisms involved in complex traits or diseases, networks are often useful tools in genetic studies: coexpression networks based on pairwise correlations between genes are commonly used. In case of a family-based design, it can be problematic when there is a large between-family variation in expression...
Article
Full-text available
Enrichment of predictive models with new biomolecular markers is an important task in high-dimensional omic applications. Increasingly, clinical studies include several sets of such omics markers available for each patient, measuring different levels of biological variation. As a result, one of the main challenges in predictive research is the inte...
Article
Full-text available
Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic...
Article
Full-text available
In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole...
Article
Full-text available
The development of immune responses is influenced by the interaction between environmental and genetic factors. Our previous study showed a close association between maternal and young infant's cytokine responses. The question is how this association evolves over time and the contribution of genetic polymorphisms to this association. Five cytokines...
Article
Full-text available
The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30...
Article
In the field of aging research, family-based sampling study designs are commonly used to study the lifespans of long-lived family members. However, the specific sampling procedure should be carefully taken into account in order to avoid biases. This work is motivated by the Leiden Longevity Study, a family-based cohort of long-lived siblings. Famil...
Article
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Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival [1] and associates with molecular markers of aging such as telomere length [2]. Understanding the underlying molecular biology of perceived age is vital...
Article
Full-text available
For people in their 40s and 50s, lifestyle programs have been shown to improve metabolic health. For older adults, however, it is not clear whether these programs are equally healthy. In the Growing Old Together study, we applied a 13-weeks lifestyle program, with a target of 12.5% caloric restriction and 12.5% increase in energy expenditure throug...
Article
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To the editor: Recent large-scale sequencing studies report recurrent somatic mutations in the blood of elderly individuals in genes previously linked to clonal expansion of hematopoietic stem cells.[1][1][⇓][2][⇓][3]-[4][4] Particularly for DNMT3A and TET2 , a steep age-associated increase in
Article
Augmentation of previously established high-dimensional predictive models with new biomolecular markers is an important task in omic applications. We introduce a two-step procedure for the assessment of the augmented predictive value of omic predictors, based on sequential double cross-validation and regularized regression models. We propose severa...
Article
Full-text available
Rapid computational and technological developments made large amounts of omics data available in different biological levels. It is becoming clear that simultaneous data analysis methods are needed for better interpretation and understanding of the underlying systems biology. Different methods have been proposed for this task, among them Partial Le...
Article
Full-text available
Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistanc...
Article
Full-text available
Reduced insulin/insulin-like growth factor 1 (IGF-1) signaling has been associated with longevity in various model organisms. However, the role of insulin/IGF-1 signaling in human survival remains controversial. The aim of this study was to test whether circulating IGF-1 axis parameters associate with old age survival and functional status in nonag...
Article
Full-text available
Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with...
Data
Discovery, replication and generalization results. Y = yes, N = no; - is negative direction, + = positive direction; weight = sample size, P = p-value; WB = whole blood.
Data
Number of genes that associate with age across all tissues. 2A: A gene-based overview for age-association across all tissues. 2B: A gene-based overview for significant expression across all tissues.
Data
Up/down regulated gene set analyses in WEBGESTALT and GENENETWORK.
Data
Transcriptomic age prediction formulas. 5A: Prediction formula weights for all participating cohorts (based on Leave-One-Out Meta-Analyses). 5B: The average "transcriptomic predictor formula" - the GENERAL predictor - for external cohorts
Data
Supplementary Figures 1-10, Supplementary Tables 1-21, Supplementary Notes 1-2, Supplementary Acknowledgements and Supplementary References
Data
Methylation results: Sobel test for methylation-based mediation of age-expression association.
Article
OBJECTIVE Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destructio...
Article
Random-effects models are often used in family-based genetic association studies to properly capture the within families relationships. In such models, the regression parameters have a conditional on the random effects interpretation and they measure, e.g., genetic effects for each family. Estimating parameters that can be used to make inferences a...
Article
Full-text available
Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-ana...
Article
Full-text available
The p16-Leiden founder mutation in the CDKN2A gene is the most common cause of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome in the Netherlands. Individuals with this mutation are at increased risk for developing melanoma of the skin, as well as pancreatic cancer. However, there is a notable interfamilial variability in the occurrence o...
Article
Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-...
Article
Full-text available
Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an...