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
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
