Genetic control of individual differences in gene-specific methylation in human brain.
paper
Cited
Public
Unavailable
- Authors
- Zhang, Dandan; Cheng, Lijun; Badner, Judith A; Chen, Chao; Chen, Qi; Luo, Wei; Craig, David W; Redman, Margot; Gershon, Elliot S; Liu, Chunyu
- Year
- 2010
- Journal
- American journal of human genetics
- PMID
- 20215007
- DOI
- 10.1016/j.ajhg.2010.02.005
- PMCID
- PMC2833385
We have observed extensive interindividual differences in DNA methylation of 8590 CpG sites of 6229 genes in 153 human adult cerebellum samples, enriched in CpG island "shores" and at further distances from CpG islands. To search for genetic factors that regulate this variation, we performed a genome-wide association study (GWAS) mapping of methylation quantitative trait loci (mQTLs) for the 8590 testable CpG sites. cis association refers to correlation of methylation with SNPs within 1 Mb of a CpG site. 736 CpG sites showed phenotype-wide significant cis association with 2878 SNPs (after permutation correction for all tested markers and methylation phenotypes). In trans analysis of methylation, which tests for distant regulation effects, associations of 12 CpG sites and 38 SNPs remained significant after phenotype-wide correction. To examine the functional effects of mQTLs, we analyzed 85 genes that were with genetically regulated methylation we observed and for which we had quality gene expression data. Ten genes showed SNP-methylation-expression three-way associations-the same SNP simultaneously showed significant association with both DNA methylation and gene expression, while DNA methylation was significantly correlated with gene expression. Thus, we demonstrated that DNA methylation is frequently a heritable continuous quantitatively variable trait in human brain. Unlike allele-specific methylation, genetic polymorphisms mark both cis- and trans-regulatory genetic sites at measurable distances from their CpG sites. Some of the genetically regulated DNA methylation is directly connected with genetically regulated gene expression variation.
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| Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. | Smith AK et al. | β | 2014 | β |
| No association between genetic or epigenetic variation in insulin growth factors and antipsychotic-induced metabolic disturbances in a cross-sectional sample. | Moons T et al. | β | 2014 | β |
| Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways. | Ong ML et al. | β | 2014 | β |
| Regulatory and coding genome regions are enriched for trait associated variants in dairy and beef cattle. | Koufariotis L et al. | β | 2014 | β |
| Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis. | Yang IV et al. | β | 2014 | β |
| Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model. | Wang F et al. | β | 2014 | β |
| Single nucleotide variations: biological impact and theoretical interpretation. | Katsonis P et al. | β | 2014 | β |
| The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. | Teh AL et al. | β | 2014 | β |
| The effects of olanzapine on genome-wide DNA methylation in the hippocampus and cerebellum. | Melka MG et al. | β | 2014 | β |
| The Influences of Genetic and Environmental Factors on Methylome-wide Association Studies for Human Diseases. | Sun YV | β | 2014 | β |
| The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts. | Wagner JR et al. | β | 2014 | β |
| Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array. | Price ME et al. | β | 2013 | β |
| Comparative DNA methylation among females with neurodevelopmental disorders and seizures identifies TAC1 as a MeCP2 target gene. | Aldinger KA et al. | β | 2013 | β |
| CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset. | Belot MP et al. | β | 2013 | β |
| Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. | Breitling LP | β | 2013 | β |
| Differential placental methylation and expression of VEGF, FLT-1 and KDR genes in human term and preterm preeclampsia. | Sundrani DP et al. | β | 2013 | β |
| DNA methylation contributes to natural human variation. | Heyn H et al. | β | 2013 | β |
| Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants. | Gamazon ER et al. | β | 2013 | β |
| Epigenetic mechanisms and models in the origins of asthma. | Karmaus W et al. | β | 2013 | β |
| Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans. | Zhang TY et al. | β | 2013 | β |
| Epigenetic signature of panic disorder: a role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? | Domschke K et al. | β | 2013 | β |
| Epigenetics in the human brain. | Houston I et al. | β | 2013 | β |
| Genetic and epigenetic regulation of human lincRNA gene expression. | Popadin K et al. | β | 2013 | β |
| Genetic effects on DNA methylation and its potential relevance for obesity in Mexican Americans. | Carless MA et al. | β | 2013 | β |
| Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. | Lencz T et al. | β | 2013 | β |
| Genome-wide association study of Tourette's syndrome. | Scharf JM et al. | β | 2013 | β |
| Genome-wide methylation profiling of the bronchial mucosa of asthmatics: relationship to atopy. | Kim YJ et al. | β | 2013 | β |
| Global properties and functional complexity of human gene regulatory variation. | Gaffney DJ | β | 2013 | β |
| Inactive or moderately active human promoters are enriched for inter-individual epialleles. | Gemma C et al. | β | 2013 | β |
| Integrative analysis of tissue-specific methylation and alternative splicing identifies conserved transcription factor binding motifs. | Wan J et al. | β | 2013 | β |
| Leukocyte DNA as surrogate for the evaluation of imprinted Loci methylation in mammary tissue DNA. | Barault L et al. | β | 2013 | β |
| Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers. | Xing C et al. | β | 2013 | β |
| Multilocus loss of DNA methylation in individuals with mutations in the histone H3 lysine 4 demethylase KDM5C. | Grafodatskaya D et al. | β | 2013 | β |
| Passive and active DNA methylation and the interplay with genetic variation in gene regulation. | Gutierrez-Arcelus M et al. | β | 2013 | β |
| Pathway analysis using information from allele-specific gene methylation in genome-wide association studies for bipolar disorder. | Chuang LC et al. | β | 2013 | β |
| Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls. | Zhang H et al. | β | 2013 | β |
| SNPs located at CpG sites modulate genome-epigenome interaction. | Zhi D et al. | β | 2013 | β |
| The expanding genomic landscape of autism: discovering the 'forest' beyond the 'trees' | Hu VW | β | 2013 | β |
| The genomic signature of trait-associated variants. | Kindt AS et al. | β | 2013 | β |
| The methylation of the LEPR/LEPROT genotype at the promoter and body regions influence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy. | Yousefi M et al. | β | 2013 | β |
| A functional methylome map of ulcerative colitis. | HΓ€sler R et al. | β | 2012 | β |
| A genetic association study of DNA methylation levels in the DRD4 gene region finds associations with nearby SNPs. | Docherty SJ et al. | β | 2012 | β |
| Alcohol-induced plasticity in the dynorphin/kappa-opioid receptor system. | Sirohi S et al. | β | 2012 | β |
| Analysing and interpreting DNA methylation data. | Bock C | β | 2012 | β |
| DNA methylation: an epigenetic risk factor in preterm birth. | Menon R et al. | β | 2012 | β |
| DNA methylation in schizophrenia: progress and challenges of epigenetic studies. | Nishioka M et al. | β | 2012 | β |
| DNA methylation signatures in development and aging of the human prefrontal cortex. | Numata S et al. | β | 2012 | β |
| DNA methylation studies using twins: what are they telling us? | Bell JT et al. | β | 2012 | β |
| Early life precursors, epigenetics, and the development of food allergy. | Hong X et al. | β | 2012 | β |
| Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight. | Pidsley R et al. | β | 2012 | β |
| Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. | Bell JT et al. | β | 2012 | β |
| Factors underlying variable DNA methylation in a human community cohort. | Lam LL et al. | β | 2012 | β |
| Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects. | van Eijk KR et al. | β | 2012 | β |
| Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12. | McKay JA et al. | β | 2012 | β |
| Genetic-epigenetic interaction modulates ΞΌ-opioid receptor regulation. | Oertel BG et al. | β | 2012 | β |
| Genetic modifiers of chromatin acetylation antagonize the reprogramming of epi-polymorphisms. | Abraham AL et al. | β | 2012 | β |
| Genetics and epigenetics of osteoarthritis. | Reynard LN et al. | β | 2012 | β |
| Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. | Hu L et al. | β | 2012 | β |
| Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates. | Wang J et al. | β | 2012 | β |
| Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life. | Wang D et al. | β | 2012 | β |
| Minireview: Epigenetics of obesity and diabetes in humans. | Slomko H et al. | β | 2012 | β |
| Natural epigenetic variation in the female great roundleaf bat (Hipposideros armiger) populations. | Liu S et al. | β | 2012 | β |
| Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence. | Gordon L et al. | β | 2012 | β |
| Population-specificity of human DNA methylation. | Fraser HB et al. | β | 2012 | β |
| Postnatal growth and DNA methylation are associated with differential gene expression of the TACSTD2 gene and childhood fat mass. | Groom A et al. | β | 2012 | β |
| Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. | Tobi EW et al. | β | 2012 | β |
| The value of twins in epigenetic epidemiology. | Bell JT et al. | β | 2012 | β |
| Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. | Relton CL et al. | β | 2012 | β |
| Use of functional genomics to identify candidate genes underlying human genetic association studies of vascular diseases. | Yang X | β | 2012 | β |
| Analysis of the GAD1 promoter: trans-acting factors and DNA methylation converge on the 5' untranslated region. | Chen Y et al. | β | 2011 | β |
| An integrative functional genomics approach for discovering biomarkers in schizophrenia. | Vawter MP et al. | β | 2011 | β |
| A twin approach to unraveling epigenetics. | Bell JT et al. | β | 2011 | β |
| DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. | Bell JT et al. | β | 2011 | β |
| Environmental regulation of the neural epigenome. | Caldji C et al. | β | 2011 | β |
| Epigenome-wide association studies for common human diseases. | Rakyan VK et al. | β | 2011 | β |
| Hypothesis: epigenetic effects will require a review of the genetics of child development. | KosztolΓ‘nyi G | β | 2011 | β |
| Integrative genomics strategies to elucidate the complexity of drug response. | Kasarskis A et al. | β | 2011 | β |
| Racial differences in gene-specific DNA methylation levels are present at birth. | Adkins RM et al. | β | 2011 | β |
| Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. | Chen C et al. | β | 2011 | β |
| Risk alleles for chronic hepatitis B are associated with decreased mRNA expression of HLA-DPA1 and HLA-DPB1 in normal human liver. | O'Brien TR et al. | β | 2011 | β |
| Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray. | Chen YA et al. | β | 2011 | β |
| Statistical approaches for the analysis of DNA methylation microarray data. | Siegmund KD | β | 2011 | β |
| T2DM: Why Epigenetics? | Fradin D et al. | β | 2011 | β |
| The importance of phase information for human genomics. | Tewhey R et al. | β | 2011 | β |
| Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism. | Andraos C et al. | β | 2011 | β |
| Allele-specific DNA methylation: beyond imprinting. | Tycko B | β | 2010 | β |
| Allele-specific methylation in the human genome: implications for genetic studies of complex disease. | Meaburn EL et al. | β | 2010 | β |
| CpG methylation in neurons: message, memory, or mask? | Sharma RP et al. | β | 2010 | β |
| Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. | Relton CL et al. | β | 2010 | β |
| Epigenetic regulation of the neural transcriptome: the meaning of the marks. | Meaney MJ et al. | β | 2010 | β |
| Epigenome mapping in normal and disease States. | Maunakea AK et al. | β | 2010 | β |
| Insights from GWAS into the quantitative genetics of transcription in humans. | Kim J et al. | β | 2010 | β |
| Role of epigenetics in Alzheimer's and Parkinson's disease. | Kwok JB | β | 2010 | β |
| The epigenomic interface between genome and environment in common complex diseases. | Bell CG et al. | β | 2010 | β |