The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
DNA Methylation Signatures in Development and Aging of the Human Prefrontal Cortex
Open accessAbstract
The human prefrontal cortex (PFC), a mastermind of the brain, is one of the last brain regions to mature. To investigate the role of epigenetics in the development of PFC, we examined DNA methylation in ∼14,500 genes at ∼27,000 CpG loci focused on 5' promoter regions in 108 subjects range in age from fetal to elderly. DNA methylation in the PFC shows unique temporal patterns across life. The fastest changes occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. At the genome level, the transition from fetal to postnatal life is typified by a reversal of direction, from demethylation prenatally to increased methylation postnatally. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes, including genes involved in brain development and in de novo DNA methylation. Our results indicate that promoter DNA methylation in the human PFC is a highly dynamic process modified by genetic variance and regulating gene transcription. Additional discovery is made possible with a stand-alone application, BrainCloudMethyl.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, at loci that changed both in fetal and postnatal periods, demethylated states predominated during fetal periods with increasing methylation observed during the postnatal period.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Numata et al., 2012
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602
Irizarry, R. A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.298 · Cited by 2,177
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084
Self-citationStability and flexibility of epigenetic gene regulation in mammalian development
Reik, W. (2007) · Nature · doi:10.1038/nature05918 · Cited by 1,963 · cited 1×
“DNA methylation at CpG dinucleotides has long been considered a key mechanism of transcriptional regulation and a critical factor in embryonic development and in cancer.(6,7) However, little is known about the normal developmental changes in DNA methylation of the human PFC, particularly during early life.”
BackgroundCapturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis
Leek, J. T., & Storey, J. D. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030161 · Cited by 1,930
Christensen, B. C., Houseman, E. A., Marsit, C. J., Zheng, S., Wrensch, M., Wiemels, J. L., Nelson, H. H., Karagas, M. R., Padbury, J. F., Bueno, R., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000602 · Cited by 1,102
Active DNA demethylation: many roads lead to Rome
Wu, S. C., & Zhang, Y. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2950 · Cited by 1,091
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., Silva, A. J., & Fan, G. (2010) · Nature Neuroscience · doi:10.1038/nn.2514 · Cited by 1,019
Development of the human cerebral cortex: Boulder Committee revisited
Bystron, I., Blakemore, C., & Rakic, P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2252 · Cited by 977
Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer
Teschendorff, A. E., Menon, U., Gentry-Maharaj, A., Ramus, S. J., Weisenberger, D. J., Shen, H., Campan, M., Noushmehr, H., Bell, C. G., Maxwell, A. P., et al. (2010) · Genome Research · doi:10.1101/gr.103606.109 · Cited by 855
Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., Jia, P., Assadzadeh, A., Flanagan, J., Schumacher, A., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.008 · Cited by 773
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
Gibbs, J. R., van der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S.-L., Arepalli, S., Dillman, A., Rafferty, I. P., Troncoso, J., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000952 · Cited by 769
Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domainsPreprint
Rakyan, V. K., Down, T. A., Maslau, S., Andrew, T., Yang, T.-P., Beyan, H., Whittaker, P., McCann, O. T., Finer, S., Valdes, A. M., et al. (2010) · Genome Research · doi:10.1101/gr.103101.109 · Cited by 746
Bhutani, N., Burns, D. M., & Blau, H. M. (2011) · Cell · doi:10.1016/j.cell.2011.08.042 · Cited by 727
Spl elements protect a CpG island from de novo methylation
Brandeis, M., Frank, D., Keshet, I., Siegfried, Z., Mendelsohn, M. M., Names, A., Temper, V., Razin, A., & Cedar, H. (1994) · Nature · doi:10.1038/371435a0 · Cited by 719
Temporal dynamics and genetic control of transcription in the human prefrontal cortex
Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., Colantuoni, E. A., Elkahloun, A. G., Herman, M. M., Weinberger, D. R., et al. (2011) · Nature · doi:10.1038/nature10524 · Cited by 685
Self-citationDNA methylation profiles in monozygotic and dizygotic twins
Kaminsky, Z. A., Tang, T., Wang, S.-C., Ptak, C., Oh, G., Wong, A. H. C., Feldcamp, L. A., Virtanen, C., Halfvarson, J., Tysk, C., et al. (2009) · Nature Genetics · doi:10.1038/ng.286 · Cited by 680
Javierre, B. M., Fernández, A. F., Richter, J., Al‐Shahrour, F., Martín-Subero, J. I., Rodríguez‐Ubreva, J., Berdasco, M., Fraga, M. F., OʼHanlon, T. P., Rider, L. G., et al. (2009) · Genome Research · doi:10.1101/gr.100289.109 · Cited by 678
Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens
LaPlant, Q., Vialou, V., Covington, H. E., Dumitriu, D., Feng, J., Warren, B. L., Maze, I., Dietz, D. M., Watts, E. L., Iñiguez, S. D., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2619 · Cited by 612
Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
Wu, H., Coskun, V., Tao, J., Xie, W., Ge, W., Yoshikawa, K., Li, E., Zhang, Y., & Sun, Y. E. (2010) · Science · doi:10.1126/science.1190485 · Cited by 604
Johnson, M. B., Kawasawa, Y. I., Mason, C. E., Krsnik, Ž., Coppola, G., Bogdanović, D., Geschwind, D. H., Mane, S. M., State, M. W., & Šestan, N. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.027 · Cited by 603
Genome-Wide Dna Methylation Profiling Using Infinium ® Assay
Bibikova, M. V., Le, J. M., Barnes, B., Saedinia-Melnyk, S., Zhou, L., Shen, R., & Gunderson, K. L. (2009) · Epigenomics · doi:10.2217/epi.09.14 · Cited by 588
Genetics of multiple sclerosis
Dyment, D. A., Ebers, G. C., & Dessa Sadovnick, A. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00663-x · Cited by 563
Developmental programming of CpG island methylation profiles in the human genome
Straussman, R., Nejman, D., Roberts, D. N., Steinfeld, I., Blum, B., Benvenisty, N., Simon, I., Yakhini, Z., & Cedar, H. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1594 · Cited by 404
Genetic Control of Individual Differences in Gene-Specific Methylation in Human Brain
Zhang, D., Cheng, L., Badner, J. A., Chen, C., Chen, Q., Luo, W., Craig, D. W., Redman, M., Gershon, E. S., & Liu, C. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.005 · Cited by 395
Distinct DNA methylation changes highly correlated with chronological age in the human brain
Hernandez, D. G., Nalls, M. A., Gibbs, J. R., Arepalli, S., van der Brug, M., Chong, S., Moore, M., Longo, D. L., Cookson, M., Traynor, B. J., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq561 · Cited by 382
Mastroeni, D., McKee, A. C., Grover, A., Rogers, J., & Coleman, P. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006617 · Cited by 298
Critical Factors in Gene Expression in Postmortem Human Brain: Focus on Studies in Schizophrenia
Lipska, B. K., Deep‐Soboslay, A., Weickert, C. S., Hyde, T. M., Martin, C. E., Herman, M. M., & Kleinman, J. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.019 · Cited by 280
Self-citationIn psychosis, cortical interneurons overexpress DNA-methyltransferase 1
Veldić, M., Guidotti, A., Maloku, E., Davis, J. M., & Costa, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409665102 · Cited by 269
A Study of the Influence of Sex on Genome Wide Methylation
Liu, J., Morgan, M., Hutchison, K. E., & Calhoun, V. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010028 · Cited by 265
和多田, 淳. (1993) · Journal of Japan Society for Fuzzy Theory and Intelligent Informatics · doi:10.3156/jfuzzy.5.2_292_2 · Cited by 239
Tissue‐specific dysregulation of DNA methylation in aging
Thompson, R. F., Atzmon, G., Gheorghe, C. P., Liang, H. Q., Lowes, C., Greally, J. M., & Barzilai, N. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00577.x · Cited by 213
Age-Related DNA Methylation Changes in Normal Human Prostate Tissues
Kwabi‐Addo, B., Chung, W., Shen, L., Ittmann, M., Wheeler, T. M., Jelı́nek, J., & Issa, J. J. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0085 · Cited by 213
Molecular insights into human brain evolution
Hill, R. S., & Walsh, C. A. (2005) · Nature · doi:10.1038/nature04103 · Cited by 208
Common variants conferring risk of schizophrenia: A pathway analysis of GWAS data
Jia, P., Wang, L., Meltzer, H. Y., & Zhao, Z. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.07.001 · Cited by 202
Kuratomi, G., Iwamoto, K., Bundo, M., Kusumi, I., Kato, N., Iwata, N., Ozaki, N., & Kato, T. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002001 · Cited by 189
Fidelity of the Methylation Pattern and Its Variation in the GenomePreprint
Ushijima, T., Watanabe, N., Okochi, E., Kaneda, A., Sügimura, T., & Miyamoto, K. (2003) · Genome Research · doi:10.1101/gr.969603 · Cited by 174
DNA methylation in early development
Geiman, T. M., & Muegge, K. (2009) · Molecular Reproduction and Development · doi:10.1002/mrd.21118 · Cited by 132
Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis
Need, A. C., Keefe, R. S. E., Ge, D., Grossman, I., Dickson, S., McEvoy, J. P., & Goldstein, D. B. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.264 · Cited by 96
Chen, Y.-A., Choufani, S., Ferreira, J. C., Grafodatskaya, D., Butcher, D. T., & Weksberg, R. (2011) · Genomics · doi:10.1016/j.ygeno.2010.12.004 · Cited by 90
Kleinman, J. E., Law, A. J., Lipska, B. K., Hyde, T. M., Ellis, J. K., Harrison, P. J., & Weinberger, D. R. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.10.032 · Cited by 89
Self-citationDNA methylation changes in schizophrenia and bipolar disorder
Connor, C., & Akbarian, S. (2008) · Epigenetics · doi:10.4161/epi.3.2.5938 · Cited by 84
Inactive X chromosome-specific reduction in placental DNA methylation
Cotton, A. M., Avila, L., Peñaherrera, M. S., Affleck, J. G., Robinson, W. P., & Brown, C. J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp299 · Cited by 82
Epigenetic Inactivation of the Groucho Homologue Gene TLE1 in Hematologic Malignancies
Fraga, M. F., Berdasco, M., Ballestar, E., Ropero, S., López‐Nieva, P., Lopez‐Serra, L., Martín-Subero, J. I., Calasanz, M. J., de Silanes, I. L., Setién, F., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0085 · Cited by 52
Neurodevelopmental Origins of Schizophrenia
Weinberger, D. R., & Levitt, P. R. (2010) · Wiley eBooks · doi:10.1002/9781444327298.ch19 · Cited by 49
Self-citationBuscarlet, M., Perin, A., Laing, A. F., Brickman, J. M., & Stifani, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800722200 · Cited by 41
Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
Xin, Y., Chanrion, B., Liu, M.-M., Galfalvy, H., Costa, R., Ilievski, B., Rosoklija, G. B., Arango, V., Dwork, A. J., Mann, J. J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011357 · Cited by 39
Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma
Revill, K., Dudley, K. J., Clayton, R. N., McNicol, A. M., & Farrell, W. E. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0008 · Cited by 37
Active DNA demethylation: the enigma starts in the zygote
Arand, J., Lepikhov, K., Wossidlo, M., & Walter, J. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9780511777271.011 · Cited by 3
Cited by
Sorted by citations
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830
Chen, Y. A., Lemire, M., Choufani, S., Butcher, D. T., Grafodatskaya, D., Zanke, B. W., Gallinger, S., Hudson, T. J., & Weksberg, R. (2013) · Epigenetics · doi:10.4161/epi.23470 · Cited by 1,547
Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci
De Jager, P. L., Srivastava, G., Lunnon, K., Burgess, J., Schalkwyk, L. C., Yu, L., Eaton, M. L., Keenan, B. T., Ernst, J., McCabe, C., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3786 · Cited by 956
“8,10-12 In this study, we present the results of a statistically rigorous gene discovery effort to identify regions of the genome that are differentially methylated in relation to the burden of AD neuropathology.”
DNA methylation and healthy human aging
Jones, M. J., Goodman, S. J., & Kobor, M. S. (2015) · Aging Cell · doi:10.1111/acel.12349 · Cited by 973
Metadata
- Authors
- Numata, S., Ye, T., Hyde, T. M., Guitart-Navarro, X., Tao, R., Wininger, M., Colantuoni, C., Weinberger, D. R., Kleinman, J. E., & Lipska, B. K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lipska, Barbara K.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 90
- Issue
- 2
- Pages
- 260-272
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC3276664
- OpenAlex
- W1994872818
- Cited by
- 364
- References
- 54
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 25 · 2021: 24 · 2020: 21 · 2019: 21 · 2018: 28 · 2017: 29 · 2016: 44 · 2015: 36 · 2014: 34 · 2013: 46 · 2012: 22
- FWCI
- 17.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- National Human Genome Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, prefrontal cortex, brain development, brain aging, promoter methylation, CpG sites, genetic variants, gene expression regulation, de novo methylation
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Female, Fetus, Humans, Infant, Infant, Newborn, Male, Middle Aged, Promoter Regions, Genetic, Sex Factors, Genetic Variation, Prefrontal Cortex, CpG Islands, DNA Methylation, Quantitative Trait Loci, Epigenesis, Genetic, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
