Wibowo Arindrarto
A5063747411- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Birth, Development, and Health
- Cancer-related molecular mechanisms research
- Genetic Syndromes and Imprinting
- Gene expression and cancer classification
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- Muscle Physiology and Disorders
- Renal and related cancers
- Venous Thromboembolism Diagnosis and Management
- Single-cell and spatial transcriptomics
- Marine Ecology and Invasive Species
- Genetics and Neurodevelopmental Disorders
- Health, Environment, Cognitive Aging
- Genomics and Chromatin Dynamics
- Planarian Biology and Electrostimulation
- Genetics, Bioinformatics, and Biomedical Research
- Reproductive Biology and Fertility
- Genetic Mapping and Diversity in Plants and Animals
- Biomedical Text Mining and Ontologies
Leiden University Medical Center
2015-2024
Genome Institute of Singapore
2016-2018
Hubrecht Institute for Developmental Biology and Stem Cell Research
2016
University Medical Center Utrecht
2016
Eijkman Institute for Molecular Biology
2012
Summary While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear. To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals the eQTLGen Consortium. We observed that cis -eQTLs can be detected for 88% of studied genes, but they a different genetic architecture compared to variants, limiting our ability use pinpoint...
Abstract The methylome is subject to genetic and environmental effects. Their impact may depend on sex age, resulting in sex- age-related physiological variation disease susceptibility. Here we estimate the total heritability of DNA methylation levels whole blood variance explained by common single nucleotide polymorphisms at 411,169 sites 2,603 individuals from twin families, establish a catalogue between-individual methylation. Heritability estimates vary across genome (mean=19%)...
Abstract Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most these overlap expression QTLs, indicating potential involvement in regulation gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and traits exposures, simultaneously. Applied to 43 human phenotypes, it...
We tested whether DNA-methylation profiles account for inter-individual variation in body mass index (BMI) and height they predict these phenotypes over above genetic factors. Genetic predictors were derived from published summary results the largest genome-wide association studies on BMI (n ∼ 350,000) 250,000) to date. methylation by estimating probe-trait effects discovery samples them external samples. Methylation associated with older individuals Lothian Birth Cohorts (LBCs, n = 1,366)...
Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted targeted therapy. Genetic in AML are structurally diverse currently detected different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, flexible platform for diagnostics. We developed HAMLET (Human Expedited Transcriptomics) bioinformatics pipeline simultaneous detection fusion genes, small variants,...
Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level datasets. The development of methods that can harness is valuable enable in broader settings enhance power due increased sample size. Thus, we develop a framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) adapts multiple polygenic risk score (PRS) estimate weights from conducts an omnibus TWAS. We show practical powerful tool by both...
BackgroundSmoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of from in utero exposure, and effects environmental tobacco smoke (ETS).MethodsWe meta-analysed up to 15,014 adults across 5 cohorts with measured blood using Illumina's EPIC array for current (2560 exposed), quit < 1 year (500 (286 ETS exposure (676 exposed). We also evaluated the interaction diet (fibre,...
Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci one or of these diseases. As 90% AID-associated SNPs are intergenic intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 that associated with AID using transcriptomic data from 629 blood samples. were able 71 (39%) AID-SNPs two nearby genes, providing evidence for part multiple exist. While 54 shared by AID, 17% them do not share...
Educational attainment is a key behavioural measure in studies of cognitive and physical health, socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) identified 58 associated with educational loci characterized by pleiotropic functions shared neuronal, immune developmental processes. Associations overlapped those for smoking behaviour, but remained after accounting many CpGs: Effect sizes were on average 28% smaller genome-wide significant 11 adjusting 62% never...
Abstract Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) Ala55Val (C > T) (rs660339) single nucleotide (SNPs) with obesity, high fasting plasma glucose, serum lipids in a Balinese population. Methods A total 603 participants (278 urban 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting glucose...
In contrast to mouse, human female germ cells develop asynchronously. Germ transition meiosis, erase genomic imprints, and reactivate the X chromosome. It is unknown if these events all appear asynchronously, how they relate each other. Here we combine exome sequencing of fetal maternal tissues with single-cell RNA-sequencing five donors. We reconstruct full parental haplotypes quantify changes in allele-specific expression, genome-wide. First distinguish primordial (PGC), pre-meiotic,...
The regeneration-capable flatworm Macrostomum lignano is a powerful model organism to study the biology of stem cells in vivo. As amenable transgenesis, it complements historically used planarian models, such as Schmidtea mediterranea. However, information on transcriptome and markers M. limited. We generated de novo assembly performed first comprehensive characterization gene expression proliferating lignano, represented by somatic cells, called neoblasts, germline cells. Knockdown selected...
Abstract Background DNA methylation is a key epigenetic modification in human development and disease, yet there limited understanding of its highly coordinated regulation. Here, we identify 818 genes that affect patterns blood using large-scale population genomics data. Results By employing genetic instruments as causal anchors, establish directed associations between gene expression distant levels, while ensuring specificity the by correcting for linkage disequilibrium pleiotropy among...
Objective Multiple single‐nucleotide polymorphisms ( SNP s) conferring susceptibility to osteoarthritis OA ) mark imbalanced expression of positional genes in articular cartilage, reflected by unequally expressed alleles among heterozygotes (allelic imbalance [ AI ]). We undertook this study explore the cartilage transcriptome from patients for events identify putative disease‐driving genetic variation. Methods was assessed 42 preserved and 5 lesioned samples (from Research Arthritis...
Abstract Integrating multi-omics data into predictive models has the potential to enhance accuracy, which is essential for precision medicine. In this study, we developed interpretable by employing neural networks informed prior biological knowledge, referred as visible networks. These offer insights decision-making process and can unveil novel perspectives on underlying mechanisms associated with traits complex diseases. We tested performance, interpretability generalizability inferring...
Skeletal muscle fibrosis and impaired regeneration are major contributors to wasting in Duchenne muscular dystrophy (DMD). Muscle growth is negatively regulated by myostatin (MSTN) activins. Blockage of these pathways may improve quality function DMD. Antisense oligonucleotides (AONs) were designed specifically block the ALK4, a key receptor for MSTN/activin pathway skeletal muscle. AON-induced exon skipping resulted specific Alk4 down-regulation, inhibition MSTN activity, increased my...
Oct4 and Sox2 regulate the expression of target genes such as