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Start Over Author "Dekkers, K.F." Topic 03 medical and health sciences
3 results on '"Dekkers, K.F."'

1. Genome-wide identification of directed gene networks using large-scale population genomics data

Author

Luijk, R., Dekkers, K.F., Iterson, M. van, Arindrarto, W., Claringbould, A., Hop, P., Boomsma, D.I., Duijn, C.M. van, Greevenbroek, M.M.J. van, Veldink, J.H., Wijmenga, C., Franke, L., Hoend, P.A.C. 't, Jansen, R., Meurs, J. van, Mei, H.L., Slagboomi, P.E., Heijmans, B.T., Zwet, E.W. van, BIOS Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Epidemiology, Internal Medicine, Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Methodology

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Linkage disequilibrium, ENDOGENOUS RETROVIRUSES, Transcription, Genetic, ZAC1, Gene regulatory network, General Physics and Astronomy, Gene Expression, Genome, Linkage Disequilibrium, Population genomics, Cohort Studies, 0302 clinical medicine, Gene Regulatory Networks, RNA-SEQ, lcsh:Science, Regulator gene, education.field_of_study, 0303 health sciences, Multidisciplinary, TRANSCRIPTIONAL REGULATION, Zinc Fingers, ASSOCIATION, APOPTOSIS, Phenotype, Proto-Oncogene Proteins c-bcl-2, MENDELIAN RANDOMIZATION, EXPRESSION, Genotype, Science, Population, Genomics, Computational biology, Biology, HUMAN TISSUES, INSULIN-SECRETION, General Biochemistry, Genetics and Molecular Biology, Article, Minor Histocompatibility Antigens, 03 medical and health sciences, Mendelian randomization, Endopeptidases, Humans, HAIR, education, Gene, 030304 developmental biology, Sequence Analysis, RNA, Gene Expression Profiling, TRANS-EQTLS, Epistasis, Genetic, General Chemistry, Gene expression profiling, 030104 developmental biology, Genetics, Population, Gene Expression Regulation, CELL-DEATH, SAMPLE-SIZE, lcsh:Q, Metagenomics, Transcriptome, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P, Identification of causal drivers behind expression is essential for understanding gene function. Here authors develop a method for the large-scale inference of gene–gene interactions in observational population genomics data and characterize a network of trans-effects for 6600 genes.

Published
2018

2. Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis

Author

Mandaviya, P.R., Aissi, D., Dekkers, K.F., Joehanes, R., Kasela, S., Truong, V., Stolk, L., Heemst, D. van, Ikram, M.A., Lindemans, J., Slagboom, P.E., Tregouet, D.A., Uitterlinden, A.G., Wei, C., Wells, P., Gagnon, F., Greevenbroek, M.M.J. van, Heijmans, B.T., Milani, L., Morange, P.E., Meurs, J.B.J. van, Heil, S.G., BIOS Consortium, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Toronto, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Leiden University Medical Center (LUMC), Universiteit Leiden, Ottawa Hospital Research Institute, The Estonian Genome Center, University of Tartu, Fibrinolyse et Pathologie Vasculaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ALESSI, Marie-Christine, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinical Chemistry, Internal Medicine, and Epidemiology

Subjects
0301 basic medicine, Male, Cancer Research, Homocysteine, SMOOTH-MUSCLE-CELLS, FOLIC-ACID, 030204 cardiovascular system & hematology, Epigenesis, Genetic, chemistry.chemical_compound, 0302 clinical medicine, Leukocytes, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, DNA methylation, S-ADENOSYLHOMOCYSTEINE, VASCULAR-DISEASE, Tenascin, Methylation, RANDOMIZED CONTROLLED-TRIAL, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, LIM Domain Proteins, Fatty Acid Transport Proteins, Basic-Leucine Zipper Transcription Factors, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, ESTROGEN-RECEPTOR-ALPHA, Biology, 03 medical and health sciences, 450 k array, Chromosome 19, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, Epigenetics, DMP, DMR, GENOME-WIDE, association, Chromosome, Epigenome, homocysteine, Molecular biology, LIM PROTEIN, Activating Transcription Factor 6, meta-analysis, 030104 developmental biology, chemistry, MYOCARDIAL-INFARCTION, PLASMA HOMOCYSTEINE, epigenome-wide analysis, DNA hypomethylation, Genome-Wide Association Study
Abstract

International audience; Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes.Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis.Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methy-lated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6.Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

Published
2017

3. Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, K.F., Iterson, M. van, Slieker, R.C., Moed, M.H., Bonder, M.J., Galen, M. van, Mei, H.L., Zhernakova, D.V., Berg, L.H. van den, Deelen, J., Dongen, J. van, Heemst, D. van, Hofman, A., Hottenga, J.J., Kallen, C.J.H. van der, Schalkwijk, C.G., Stehouwer, C.D.A., Tigchelaar, E.F., Uitterlinden, A.G., Willemsen, G., Zhernakova, A., Franke, L., Hoen, P.A.C. 't, Jansen, R., Meurs, J. van, Boomsma, D.I., Duijn, C.M. van, Greevenbroek, M.M.J. van, Veldink, J.H., Wijmenga, C., Zwet, E.W. van, Slagboom, P.E., Jukema, J.W., Heijmans, B.T., BIOS Consortium, Amsterdam Neuroscience - Complex Trait Genetics, Biological Psychology, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Epidemiology, Internal Medicine, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology and Data Science, Laboratory Medicine, and Psychiatry

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Blood lipids, 030204 cardiovascular system & hematology, Biology, Bioinformatics, Epigenesis, Genetic, NORMALIZATION, lipids, Random Allocation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MICROARRAY, Mendelian randomization, Journal Article, Humans, EPIDEMIOLOGY, Epigenetics, CPT1A LOCUS, POPULATION, EPIGENOME-WIDE ASSOCIATION, Molecular Epidemiology, DNA methylation, PLASMA, Cholesterol, Research, CHOLESTEROL, Mendelian Randomization Analysis, Lipid metabolism, 3. Good health, Phenotype, 030104 developmental biology, chemistry, ATHEROSCLEROSIS, lipids (amino acids, peptides, and proteins), Gene expression, Lipoprotein
Abstract

Background Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals. Results This analysis shows that differential methylation is the consequence of inter-individual variation in blood lipid levels and not vice versa. Specifically, we observe an effect of triglycerides on DNA methylation at three CpGs, of LDL cholesterol at one CpG, and of HDL cholesterol at two CpGs using multivariable Mendelian randomization. Using RNA-seq data available for a large subset of individuals (N = 2044), DNA methylation of these six CpGs is associated with the expression of CPT1A and SREBF1 (for triglycerides), DHCR24 (for LDL cholesterol) and ABCG1 (for HDL cholesterol), which are all key regulators of lipid metabolism. Conclusions Our analysis suggests a role for epigenetic priming in end-product feedback control of lipid metabolism and highlights Mendelian randomization as an effective tool to infer causal relationships in integrative genomics data. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1000-6) contains supplementary material, which is available to authorized users.

Published
2016

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