EGAGenomicsIllumina HiSeq 2500Otherhttps://ega-archive.org/studies/EGAS00001001099EGAEGA study EGAS00001001099Whole genome MeDIP-seq of DNA in whole blood samples from 5yr old Swedish children (the ABIS study)EGArestricted<h4>Background</h4>Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic link prospectively in children.<h4>Results</h4>Here, we studied a homogenous group of 48 5-year-old children. By combining hair cortisol measurements (a well-documented biomarker for chronic stress), with whole-genome DNA-methylation sequencing, we show that high cortisol associates with a genome-wide decrease in DNA methylation and targets short interspersed nuclear elements (SINEs; a type of retrotransposon) and genes important for calcium transport: phenomena commonly affected in stress-related diseases and in biological aging. More importantly, we identify a zinc-finger transcription factor, ZNF263, whose binding sites where highly overrepresented in regions experiencing methylation loss. This type of zinc-finger protein has previously shown to be involved in the defense against retrotransposons.<h4>Conclusions</h4>Our results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that this may affect future disease susceptibility by alterations in the epigenetic mechanisms that keep retrotransposons dormant. Future treatments for stress- and age-related diseases may therefore seek to target zinc-finger proteins that epigenetically control retrotransposon reactivation, such as ZNF263.High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases.Nätt Daniel D, Johansson Ingela I, Faresjö Tomas T, Ludvigsson Johnny J, Thorsell Annika AMethylated DNA Immunoprecipitation sequencing.setulae, scale tissue, Biological Markers, Viral Marker, Materials, Surrogate Endpoints, Methylated DNA Immunoprecipitation sequencing, 21-trihydroxy-, Laboratory, acetylglucosaminyltransferase-like protein, Biochemical, Mbp1, Kendall's compound F, Endpoint, Aging, Serum, CG11121, element, Hair, 11, Laboratory Markers, Donor Artificial Insemination, Readability, old, 17, diseases, Biological, CDA2, symptoms, 21-Trihydroxy-4-pregnene-3, hydrocortisonum, diseases and disorders, myd, 21-triol-3, Donor Artificial, Senescence, thymus nucleic acid, human disease, Fetal Hairs, 21-trihydroxy-4-pregnene-3, Cortef, like-acetylglucosaminyltransferase, Genomes, plant peltate hair, vibrissa, Mbp-1, Fingers, TF binding, SO, set, Biological Aging, Immune, 11 alpha)-Isomer, Markers, Fetal, Viral Markers, 11beta, Homo sapiens disease, Double-Stranded DNA, deoxyribonucleic acids, DNAn, So, (11beta)-, screening, Viral, wide/broad, Surrogate Endpoint, gyltl1b-b, Hairs, Biochemical Markers, Double-Stranded, Biologic Marker, (Deoxyribonucleotide)n+m, Marker, MDDGA6, mKIAA0609, Cortril, Diseases, (9 beta, anxiety, Heterologous Insemination, Genetic Materials, atomo, desoxyribose nucleic acid, atome, KIAA0609, Genetic Material, acetylglucosaminyltransferase-like 1A, fg, whisker, Element, gyltl1b, End Points, atoms, 20-dione, mdc1d, signs, whole genome, Immunologic, Laboratory Marker, Children, LARGE_HUMAN, MDC1D, disease, Artificial Insemination, wide, Finger, Epicortisol, enr, Biochemical Marker, Material, ds DNA, Cistron, medical 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II core promoter proximal region sequence-specific binding, Circulatory system disease NOS (disorder), MDG1, Pathway, preventive therapy, Viral, sequencing_assay, Index, fore digit, Need, Endogenous, Hairs, zincum, Retain, disease of subdivision of hemolymphoid system, digit, Zn2+, Depressive Symptom, Marker, (9 beta, anxiety, atomo, sarcoglycan, Emotional, cinc, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, desoxyribose nucleic acid, atome, CARDIOVASC DIS, Symptoms, End Points, Definite Attribution, atoms, 20-dione, Disorder of the circulatory system, manual digit (phalangeal portion) plus soft tissue, F14P3_4, [X]Other ill-defined heart diseases (disorder), Immunologic, whole genome, Laboratory Marker, Children, Transcription factor, AGE, diatheses, Material, 35kD dystrophin-associated glycoprotein, ILL-DEFINED HRT DIS NEC, ds DNA, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II 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disorder, Higher, Pediatric, Paraphrenia, Transcription, Clinical, Retrovirus-like Element, Neurosis, Target, Double Stranded, Other forms of heart disease, Former, Deoxyribonucleic acid, Other specified pericardial disease NOS, Symptom, Sequencing, cardiovascular disease, Reactivation, Transposons, Zink, quill, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, Syndrome, Defense, hidrocortisona, 10 alpha, (Deoxyribonucleotide)m, Combining Sites, Methylations, atom, Biologic, OTHER SEQUELAE OF MI NEC, Drl, fur, grupo, Cortisol, 35 kDa dystrophin-associated glycoprotein, 17alpha, DNAn+1, Affects, Involutional Psychoses, Serum Markers, Proteins, disorders, changes in DNA methylation, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, Disease affecting entire cardiovascular system (disorder), SGCG, Mdu, 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Definitely Related to Intervention, Adverse Event Related to Intervention, Adults, Genetic Material, CIRCULATORY DISEASE NOS, F14P3.4, whisker, Element, Factors, Nucleic Acid Sequencing, Epigenetic, Preschool Only, Adverse Cardiac Events, Retrovirus like Elements, Retroelement, gamma (35kDa dystrophin-associated glycoprotein), DEPRESSIVE DIS MAJOR, Treatments, disease, wide, DMDA, Depressive Syndromes, Finger, Syndromes, Epicortisol, Preschool Completion, Depression, Depressive Syndrome, Biochemical Marker, Cistron, molecular pathway, short, Sequence Analysis, Methylation, hand digit, metal ion regulated proximal promoter sequence-specific DNA binding, Gruppe, Cardiovascular Disorders, other disease, ASCVD, Important, SGCG_HUMAN, Clinical Markers, Other heart disease (disorder), Importance, Gene, disease susceptibilities, major depressive disorder 2, broad, major depressive disorder 1, TYPE, Deoxyribonucleic acids, Surrogate End Points, DAGA4, [X]Cardiovascular disease, Surrogate 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2-epimerase, Certain, medical condition, Binding Site, 11-Epicortisol, Cistrons, Related Attribution, 17-hydroxycorticosterone, Other ill-defined heart disease, group, LGMD2C, transcription factor activity, Pregn-4-ene-3, Cardiac Events, Protein, Phenomena, atomus, Nuclear, methylation, ds-DNA, Other forms of heart disease (disorder), Retrovirus-like Elements, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, DEPRESSIVE DIS, PERICARDIAL DISEASE NEC, KNOTTED1-like homeobox gene 5, Depressive Disorders, Serum Marker, Depressive Neurosis, Rest, hair, MDG1 Retrotransposons, copper ion regulated core promoter proximal region sequence-specific binding, Surrogate Marker, introduction, NUCLEIC ACID SEQUENCING, Susceptibilities, Cardiovascular Disease, Specified, Protein Gene Products, 21-trihydroxypregn-4-ene-3, Other specified pericardial disease NOS (disorder), Preschool, Therapeutic, digitus manus, SCARMD2, renin-binding protein, Treatment, Major Adverse Cardiac Events, Major Depressive, Future, forelimb digit, groupe, Positive MarginsfalseABIS 1 MeDIP-seqWe investigated changes in whole genome DNA-methylation in a group of 48 healthy five-year-old children differentiated by their hair cortisol levels. By combining this novel biomarker for chronic stress with methylated DNA immunoprecipitation sequencing (MeDIP-seq), we found that high cortisol were associated with a genome-wide decrease in DNA-methylation targeted to specific zinc finger transcription factor binding sites, repetitive elements and genes important for neurodevelopment and calcium transport. Large scale hypomethylation of repetitive regions, as well as a deficient calcium transport, have been reported in many stress related diseases, as well as in many cancers and biological aging. Thus our findings may aid in our understanding of how susceptibility to these diseases develops.2017-07-26 15:39:26EGAS00001001099960626339299EGAD00001001221EGAC00001000281