Peter Henneman

Peter Henneman
Academisch Medisch Centrum Universiteit van Amsterdam | AMC · Department of Clinical Genetics, genome diagnostic laboratory

PhD

About

170
Publications
18,228
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7,296
Citations
Additional affiliations
January 2005 - October 2012
Leiden University Medical Centre
Position
  • PostDoc Position

Publications

Publications (170)
Article
Full-text available
Methylation tests have been used for decades in regular DNA diagnostics focusing primarily on Imprinting disorders or specific loci annotated to specific disease associated gene promotors. With the introduction of DNA methylation (DNAm) arrays such as the Illumina Infinium HumanMethylation450 Beadchip array or the Illumina Infinium Methylation EPIC...
Poster
Full-text available
References 1. Verberne EA, Goh S, England J, van Ginkel M, Rafael-Croes L, et al. JARID2 Haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome. Genet Med. 2021;23(2):374-83.
Article
Aim: To detect expression quantitative trait methylation (eQTM) loci within the cerebrum of prenatal Down syndrome (DS) and controls. Material & methods: DNA methylation gene expression profiles were acquired from NeuN+ nuclei, obtained from cerebrum sections of DS and controls. Linear regression models were applied to both datasets and were subseq...
Article
Full-text available
Background Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with t...
Article
Background While Vedolizumab (VDZ) is an established treatment for Crohn’s disease (CD), primary non-response is well-recognised – there is an urgent clinical need for biomarkers that predict response, before initiation of treatment. Metabolomic profiling is a rapidly growing field in biomarker discovery and can distinguish between active and quies...
Article
Background Despite the proven efficacy of vedolizumab (VDZ), only 29% and 36% of the Crohn’s disease (CD) patients present corticosteroid-free clinical- and endoscopic remission, respectively. Therefore, predictive biomarkers for treatment success would be of extreme value. Previous studies have identified aberrant DNA methylation associated with C...
Article
Background Crohn’s disease (CD) is a complex disease where the gut microbiome plays an important role. One of the established treatments in CD is Vedolizumab (VDZ), an alpha(4)beta(7) integrin antibody. Finding biomarkers to predict therapy response is still a clinical unmet need, since this treatment has shown endoscopic remission in only a third...
Article
Full-text available
Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we...
Article
Full-text available
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated...
Article
Full-text available
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate...
Article
Full-text available
Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were...
Article
Full-text available
Background Migraine is a common brain disorder but reliable diagnostic biomarkers in blood are still lacking. Our aim was to identify, using proton nuclear magnetic resonance (¹H-NMR) spectroscopy, metabolites in serum that are associated with lifetime and active migraine by comparing metabolic profiles of patients and controls. Methods Fasting se...
Article
Full-text available
Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study we...
Article
Background: Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. Methods: In this st...
Article
Full-text available
Background: African populations are experiencing health transitions due to rapid urbanization and international migration. However, the role of biological aging in this emerging burden of cardiometabolic diseases (CMD) among migrant and non-migrant Africans is unknown. We aimed to examine differences in epigenetic age acceleration (EAA) as measure...
Article
Full-text available
Aim: We assessed epigenome-wide DNA methylation (DNAm) differences between migrant and non-migrant Ghanaians. Materials & methods: We used the Illumina Infinium® HumanMethylation450 BeadChip to profile DNAm of 712 Ghanaians in whole blood. We used linear models to detect differentially methylated positions (DMPs) associated with migration. We perfo...
Article
Full-text available
In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease...
Article
Full-text available
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation data. We performed recursive ensemble feature selection (REFS)...
Article
Full-text available
Purpose We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested. Methods We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories...
Article
Full-text available
Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the...
Article
Full-text available
Background Familial hypercholesterolemia (FH) is a monogenic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C). A FH causing genetic variant in LDLR, APOB, or PCSK9 is not identified in 12–60% of clinical FH patients (FH mutation-negative patients). We aimed to assess whether altered DNA methylation might be associated...
Article
Full-text available
Histone deacetylases (HDACs) are a group of enzymes that control histone deacetylation and bear potential to direct expression of large gene sets. We determined the effect of HDAC inhibitors (HDACi) on human monocytes and macrophages, with respect to their polarization, activation, and their capabilities of inducing endotoxin tolerance. To address...
Preprint
Full-text available
Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. Therefore, we combine genome-wide...
Preprint
Full-text available
SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn's disease (CD), suggesting a role in inflammation. We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 funct...
Article
Full-text available
Crohn’s disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate the inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating m...
Article
Full-text available
Sub-Saharan African (SSA) migrants in Europe experience psychosocial stressors, such as perceived discrimination (PD). The effect of such a stressor on health could potentially be mediated via epigenetics. In this study we performed an epigenome-wide association study (EWAS) to assess the association between levels of PD with genome-wide DNA methyl...
Article
Full-text available
Autologous transplantation of spermatogonial stem cells is a promising new avenue to restore fertility in infertile recipients. Expansion of the initial spermatogonial stem cell pool through cell culturing is a necessary step to obtain enough cells for effective repopulation of the testis after transplantation. Since in vitro propagation can lead t...
Preprint
Full-text available
Crohn's disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating monoc...
Article
Full-text available
Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called “episignatures”). Peripheral blood episignatures can be...
Poster
Background While the use of biologicals has revolutionised the treatment of Crohn’s disease (CD) in recent decades, many patients fail to respond or lose response over time. Predictors for treatment selection and/or success are lacking. Vedolizumab (VDZ) induces corticosteroid-free clinical remission in 29% and endoscopic remission in 36% of patien...
Poster
Full-text available
Background SP140 (Speckled 140 KDa) encodes an epigenetic reader protein with an immune restricted expression, that binds to epigenetically modified (acetylated and methylated) histones and thereby regulates expression of large gene sets, including pro-inflammatory cytokines, in innate immune cells. SP140 is implicated in CD because single nucleoti...
Article
Full-text available
Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analy...
Article
Full-text available
Objective: In the advent of rapid urbanization, migration and epidemiological transition, the extent to which serum uric acid (sUA) affects cardiovascular disease (CVD) risk among Africans is not well understood. We assessed differences in sUA levels and associations with CVD risk among migrant Ghanaians in Europe, and non-migrant Ghanaians in rur...
Article
Full-text available
SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability...
Article
Objective In the advent of rapid urbanization, migration and epidemiological transition, the extent to which serum uric acid (sUA) affects cardiovascular disease (CVD) risk among Africans is not well understood. We assessed differences in sUA levels and associations with estimated CVD risk among migrant Ghanaians in Europe, and non-migrant Ghanaian...
Article
Background Exposure to adverse conditions earlier in life-course can predispose to type 2 diabetes in adulthood, irrespective of body mass index (BMI). However, the burden of type 2 diabetes in lean Africans is not well understood despite higher exposure to adverse early life conditions. Mirroring ongoing epidemiological transition, we assessed the...
Article
Full-text available
Purpose of Review The metabolic syndrome is a pathological state in which one of the key components is insulin resistance. A wide spectrum of body compartments is involved in its pathophysiology. Genetic and environmental factors such as diet and physical activity are both related to its etiology. Reversible modulation of gene expression without al...
Article
Full-text available
Beckwith-Wiedemann syndrome (BWS) is caused due to the disturbance of imprinted genes at chromosome 11p15. The molecular confirmation of this syndrome is possible in approximately 85% of the cases, whereas in the remaining 15% of the cases, the underlying defect remains unclear. The goal of our research was to identify new epigenetic loci related t...
Article
Full-text available
Aim: Fetal alcohol spectrum disorder (FASD) involves prenatal growth delay, impaired facial and CNS development and causes severe clinical, social-economic burdens. Here, we aim to detect DNA-methylation aberrations associated with FASD and potential FASD diagnostic and prognostic biomarkers. Patients & methods: The FASD diagnosis was established a...
Preprint
Full-text available
Macrophages are heterogeneous multifunctional leukocytes which are regulated in a tissue- and disease-specific context. Many different studies have been published using in vitro macrophage models to study disease. Here, we aggregated public expression data to define consensus expression profiles for eight commonly-used in vitro macrophage models. A...
Article
Full-text available
Background The chronic remitting and relapsing intestinal inflammation characteristic of Crohn’s disease frequently leads to fibrosis and subsequent stenosis of the inflamed region. Approximately a third of all Crohn’s disease patients require resection at some stage in their disease course. As the pathogenesis of Crohn’s disease associated fibrosi...
Data
Summary plots of the DMEGs. (A) WNT2B, (B) SERPINF1, (C) MBP, (D) FGFR4, (E) APOE, (F) ACVRL1, (G) FGFR1, (H) ZFP36L1, and (I) E2F7. At the top: Genomic coordinates at the top represent the chromosome and the genomic positions of the DMRs with the gene of interest highlighted in red. Bottom left: Detailed genome plot of the methylation values of th...
Data
Overlapping samples. An overview of all the samples included in the methylation and expression studies. Details include the sample, patient, and passage number. Samples that were included in both the methylation and expression study are shown in bold text. (XLSX)
Data
Differentially methylated regions. Differentially methylated regions as found for CD vs non-CD (Tab 1), CD-inflamed vs CD-non-inflamed (Tab 2), and CD-stenotic vs CD-non-inflamed (Tab 3). Columns represent the coordinates of the DMR, the number of CpGs encompassed, the Stouffer statistic that represents a summary significance statistic of the DMR,...
Data
DMR pathway enrichment. Columns represent the database, the gene set ID, the description of the gene set, the enrichment p-value, the BH-adjusted p-value, the number of genes within the set, the number of observed genes from the set, the average gene length of the genes within the set, the Entrez IDs for the genes located in the gene set. Tab 1: CD...
Data
DMEGs: Differentially methylated and expressed genes as found for STEN vs NINF. Columns represent the coordinates of the DMR, the associated gene name, the number of CpGs encompassed by the DMR, the Ensembl gene ID, the Entrez ID, the methylation-expression Pearson correlation coefficient alongside the 95% confidence intervals, the p-value of the c...
Data
Volcano plot of the genes measured through RNAseq experiment. The y-axis depicts the statistical significance (-log10(p-value)) and the x-axis the log2 fold change. (A) CD versus non-CD, (B) INF versus NINF, and (C) STEN vs NINF. Colors indicate whether a gene is differentially expressed with a large effect size (logFC > 1; ‘sig. interesting’), dif...
Data
Differentially expressed genes. Differentially expressed genes as found for the CD vs non-CD (Tab 1), CD-inflamed vs CD-non-inflamed (Tab 2), and CD-stenotic vs CD-non-inflamed (Tab 3). Columns represent the log2 fold change, the standard error of the log2 fold change, the Wald statistic, the p-value, the BH-adjusted p-value, the gene symbol, the E...
Data