Skip to main content Accessibility help
×
Home
Hostname: page-component-568f69f84b-d8fc5 Total loading time: 0.281 Render date: 2021-09-20T03:24:18.257Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity

Published online by Cambridge University Press:  05 February 2016

Elisa A. Esposito
Affiliation:
University of Minnesota Institute of Child Development Widener University
Meaghan J. Jones
Affiliation:
University of British Columbia Child and Family Research Institute
Jenalee R. Doom
Affiliation:
University of Minnesota Institute of Child Development
Julia L MacIsaac
Affiliation:
University of British Columbia Child and Family Research Institute
Megan R. Gunnar*
Affiliation:
University of Minnesota Institute of Child Development
Michael S. Kobor
Affiliation:
University of British Columbia Child and Family Research Institute University of British Columbia
*Corresponding
Address correspondence and reprint requests to: Megan R. Gunnar, Institute of Child Development, University of Minnesota, 51 East River Road, Minneapolis, MN 55455; E-mail: gunnar@umn.edu.

Abstract

Internationally adopted adolescents who are adopted as young children from conditions of poverty and deprivation have poorer physical and mental health outcomes than do adolescents conceived, born, and raised in the United States by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US birth, and nonadopted offspring of well-educated and well-resourced parents to control for postadoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome-wide association study to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 nonadopted youth. Adopted youth averaged 22 months at adoption, and both groups averaged 15 years at testing; thus, roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell-type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell-type composition of the adopted and nonadopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 gene ontology terms, clustered in neural and developmental categories, were significantly enriched between groups.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Balakathiresan, N. S., Chandran, R., Bhomia, M., Jia, M., Li, H., & Maheshwari, R. K. (2014). Serum and amygdala microRNA signatures of posttraumatic stress: Fear correlation and biomarker potential. Journal of Psychiatry Research, 57, 6573.CrossRefGoogle ScholarPubMed
Barker, D. J. (1997). Maternal nutrition, fetal nutrition, and disease in later life. Nutrition, 13, 807813.CrossRefGoogle ScholarPubMed
Bird, A. (2007). Perceptions of epigenetics. Nature, 447, 396398.CrossRefGoogle ScholarPubMed
Borghol, N., Suderman, M., McArdle, W., Racine, A., Hallett, M., Pembrey, M., et al. (2012). Associations with early-life socio-economic position in adult DNA methylation. International Journal of Epidemiology, 41, 6274.CrossRefGoogle ScholarPubMed
Bornancin, F. (2011). Ceramide kinase: The first decade. Cell Signal, 23, 9991008.CrossRefGoogle ScholarPubMed
Bourgon, R., Gentleman, R., & Huber, W. (2010). Independent filtering increases detection power for high-throughput experiments. Proceedings of the National Academy of Sciences, 107, 95469551.CrossRefGoogle ScholarPubMed
Boyce, W. T., & Kobor, M. S. (2015). Development and the epigenome: The “synapse” of gene–environment interplay. Developmental Science, 18, 123.CrossRefGoogle ScholarPubMed
Brady, K. T., & Back, S. E. (2012). Childhood trauma, posttraumatic stress disorder, and alcohol dependence. Alcohol Research, 34, 408413.Google ScholarPubMed
Carlson, E. A., Hostinar, C. E., Mliner, S. B., & Gunnar, M. R. (2014). The emergence of attachment following early social deprivation. Development and Psychopathology, 26, 479489.CrossRefGoogle ScholarPubMed
Chami, N., & Lettre, G. (2014). Lessons and implications from genome-wide association studies (GWAS): Findings of blood cell phenotypes. Genes (Basel), 5, 5164.CrossRefGoogle ScholarPubMed
Chang, C.-C., Lin, C.-C., Hsieh, W.-L., Lai, H.-W., Tsai, C.-H., & Cheng, Y.-W. M. (2014). MicroRNA expression profiling in PBMCs: A potential diagnostic biomarker of chronic hepatitis C. Disease Markers, 2014, 367157.CrossRefGoogle ScholarPubMed
Chen, C., Grennan, K., Badner, J., Zhang, D., Gershon, E., Jin, L., et al. (2011). Removing batch effects in analysis of expression microarray data: An evaluation of six batch adjustment methods. PLos One, 6, e17238.Google ScholarPubMed
Chugani, H. T., Behen, M. E., Muzik, O., Juhasz, C., Nagy, F., & Chugani, D. C. (2001). Local brain functional activity following early deprivation: A study of postinstitutionalized Romanian orphans. NeuroImage, 14, 12901301.CrossRefGoogle ScholarPubMed
Cicchetti, D. (2013). Annual Research Review: Resilient functioning in maltreated children—Past, present, and future perspectives. Journal of Child Psychology and Psychiatry, 54, 402422.CrossRefGoogle ScholarPubMed
Coelho, R., Viola, T. W., Walss-Bass, C., Brietzke, E., & Grassi-Oliveira, R. (2014). Childhood maltreatment and inflammatory markers: A systematic review. Acta Psychiatrica Scandianvia, 129, 180192.CrossRefGoogle ScholarPubMed
Coleman, J. A., Zhu, X., Djajadi, H. R., Molday, L. L., Smith, R. S., Libby, R. T., et al. (2014). Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival. Journal of Cell Science, 127, 11381149.CrossRefGoogle ScholarPubMed
Colige, A., Nuytinck, L., Hausser, I., van Essen, A. J., Thiry, M., Herens, C., et al. (2004). Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene. Journal of Investigative Dermatology, 123, 656663.CrossRefGoogle ScholarPubMed
Colige, A., Ruggiero, F., Vandenberghe, I., Dubail, J., Kesteloot, F., Van Beeumen, J., et al. (2005). Domain and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I–III and V. Journal of Biology and Chemistry, 280, 3439734408.CrossRefGoogle ScholarPubMed
Croft, C., O'Connor, T. G., Keavene, L., Groothues, C., & Rutter, M. (2001). Longitudinal change in parenting associated with developmental delay and catch-up. Journal of Child Psychology and Psychiatry, 42, 649659.CrossRefGoogle ScholarPubMed
Davies, M. N., Volta, M., Pidsley, R., Lunnon, K., Dixit, A., Lovestone, S., et al. (2012). Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biology, 13, R43.CrossRefGoogle ScholarPubMed
Dogan, M. V., Shields, B., Cutrona, C., Gao, L., Gibbons, F. X., Simons, R., et al. (2014). The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics, 15, 151.CrossRefGoogle ScholarPubMed
Drury, S. S., Theall, K., Gleason, M. M., Smyke, A. T., De Vivo, I., Wong, J. Y., et al. (2012). Telomere length and early severe social deprivation: Linking early adversity and cellular aging. Molecular Psychiatry, 17, 719727.CrossRefGoogle ScholarPubMed
Du, P., Kibbe, W. A., & Lin, S. M. (2008). Lumi: A pipeline for processing Illumina microarray. Bioinformatics, 24, 15471548.CrossRefGoogle ScholarPubMed
Eckerle, J. K., Hill, L. K., Iverson, S., Hellerstedt, W., Gunnar, M. R., & Johnson, D. E. (2014). Vision and hearing deficits and associations with parent-reported behavioral and developmental problems in international adoptees. Maternal and Child Health, 18, 575583.CrossRefGoogle ScholarPubMed
Elliott, H. R., Tillin, T., McArdle, W. L., Ho, K., Duggirala, A., Frayling, T. M., et al. (2014). Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clinical Epigenetics, 6, 4.CrossRefGoogle ScholarPubMed
Eriksen, H. B., Biering-Sørensen, S., Lund, N., Correia, C., Rodrigues, A., Andersen, A., et al. (2014). Factors associated with thymic size at birth among low and normal birthweight infants. Journal of Pediatrics, 165, 713721.CrossRefGoogle Scholar
Essex, M. J., Boyce, T., Goldstein, L. H., Armstrong, J. M., Kraemer, H. C., & Kupfer, D. (2002). The confluence of mental, physical, social and academic difficulties in middle childhood: II. Developing the MacArthur Health and Behavior Questionnaire. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 588603.CrossRefGoogle ScholarPubMed
Essex, M. J., Boyce, W. T., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M., et al. (2013). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development, 84, 5875.CrossRefGoogle ScholarPubMed
Farré, P., Jones, M. J., Meaney, M. J., Emberly, E., Turecki, G., & Kobor, M. S. (2015). Concordant and discordant DNA methylation signatures of aging in human blood and brain. Epigenetics Chromatin, 8, 19.CrossRefGoogle ScholarPubMed
Felliti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., et al. (1998). The relationship of adult health status to childhood abuse and household dysfunction. American Journal of Preventative Medicine, 14, 245258.CrossRefGoogle Scholar
Fernald, L. C., & Grantham-McGregor, S. M. (2002). Growth retardation is associated with changes in the stress response system and behavior in school-aged Jamaican children. Journal of Nutrition, 132, 36743679.Google ScholarPubMed
Ferretti, E., De Smaele, E., Miele, E., Laneve, P., Po, A., Pelloni, M., et al. (2008). Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO Journal, 27, 26162627.CrossRefGoogle ScholarPubMed
Fleming, A. S., Kraemer, G. W., Gonzalez, A., Lovic, V., Rees, S., & Melo, A. (2002). Mothering begets mothering: The transmission of behavior and its neurobiology across generations. Pharmacology, Biochemistry and Behavior, 73, 6175.CrossRefGoogle Scholar
Garvin, M. C., Tarullo, A. R., Van Ryzin, M., & Gunnar, M. R. (2012). Post-adoption parenting and socioemotional development in postinstitutionalized children. Development and Psychopathology, 24, 3548.CrossRefGoogle Scholar
Gillis, J., Mistry, M., & Pavlidis, P. (2010). Gene function analysis in complex data sets using ErmineJ. Nature Protocols, 5, 11481159.CrossRefGoogle ScholarPubMed
Gunnar, M. R., Bruce, J., & Grotevant, H. D. (2000). International adoption of institutionally reared children: Research and policy. Development and Psychopathology, 12, 677693.CrossRefGoogle ScholarPubMed
Hellerstedt, W. L., Madsen, N. J., Gunnar, M. R., Grotevant, H. D., Lee, R. M., & Johnson, D. E. (2008). The international adoption project: Population-based surveillance of Minnesota parents who adopted children internationally. Maternal and Child Health Journal, 12, 162171.CrossRefGoogle ScholarPubMed
Hertzman, C. (1999). The biological embedding of early experience and its effects on health in adulthood. Annals of the New York Academy of Sciences, 896, 8595.CrossRefGoogle ScholarPubMed
Hertzman, C., & Boyce, T. (2010). How experience gets under the skin to create gradients in developmental health. Annual Review of Public Health, 31, 329347.CrossRefGoogle ScholarPubMed
Hodel, A. S., Hunt, R. H., Cowell, R. A., Van Den Heuvel, S. E., Gunnar, M. R., & Thomas, K. M. (2015). Duration of early adversity and structural brain development in post-institutionalized adolescents. NeuroImage. Advance online publication.CrossRefGoogle ScholarPubMed
Hou, Q., Barr, T., Gee, L., Vickers, J., Wymer, J., Borsani, E., et al. (2011). Keratinocyte expression of calcitonin gene-related peptide β: Implications for neuropathic and inflammatory pain mechanisms. Pain, 152, 20362051.CrossRefGoogle Scholar
Houseman, E. A., Accomando, W. P., Koestler, D. C., Christensen, B. C., Marsit, C. J., Nelson, H. H., et al. (2012). DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics, 13, 86.CrossRefGoogle ScholarPubMed
Humphreys, K. L., & Zeanah, C. H. (2015). Deviations from the expectable environment in early childhood and emerging psychopathology. Neuropsychopharmacology, 40, 154170.CrossRefGoogle Scholar
Illingworth, R. S., & Bird, A. P. (2009). CpG islands—“A rough guide.” FEBS Letters, 583, 17131720.CrossRefGoogle Scholar
Jaffe, A. E., & Irizarry, R. A. (2014). Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biology, 15, R31.CrossRefGoogle Scholar
Johnson, D. E., & Gunnar, M. R. (2011). Growth failure in institutionalized children. Monograph of the Society for Child Development, 76, 92126.CrossRefGoogle ScholarPubMed
Johnson, J. H., & Cutcheon, S. (1980). Assessing life events in older children and adolescents: Preliminary findings with the life events checklist. In Sarason, I. G. & Spielberger, C. D. (Eds.), Stress and anxiety (Vol. 7). Washington, DC: Hemisphere.Google ScholarPubMed
Jones, M. J., Islam, S. A., Edgar, R. D., & Kobor, M. S. (2015). Adjusting for cell type composition in DNA methylation data using a regression-based approach. Methods in Molecular Biology. Advance online publication.CrossRefGoogle ScholarPubMed
Jones, P. A. (2012). Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nature Review Genetics, 13, 484492.CrossRefGoogle ScholarPubMed
Joubert, B. R., Håberg, S. E., Nilsen, R. M., Wang, X., Vollset, S. E., Murphy, S. K., et al. (2012). 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environmental Health Perspectives, 120, 14251431.CrossRefGoogle ScholarPubMed
Koestler, D. C., Christensen, B., Karagas, M. R., Marsit, C. J., Langevin, S. M., Kelsey, K. T., et al. (2013). Blood-based profiles of DNA methylation predict the underlying distribution of cell types: A validation analysis. Epigenetics, 8, 816826.CrossRefGoogle Scholar
Kohn, J. N., Howell, B. R., Guzman, D. B., Meyer, J. S., Ibegbu, C. C., & Sanchez, M. M. (2014). Early life stress and perinatal glucocorticoid exposure produce complex immune system alterations, including accelerated T cell immunosenescence, in adolescent rhesus macaques. Brain, Behavior and Immunity, 40, e50.CrossRefGoogle Scholar
Koss, K. J., Hostinar, C. E., Donzella, B., & Gunnar, M. R. (2014). Social deprivation and the HPA axis in early development. Developmental Science, 50, 113.Google ScholarPubMed
Kumsta, R., Kreppner, J., Rutter, M., Beckett, C., Castle, J., Stevens, S., et al. (2010). III. Deprivation-specific psychological patterns. Monographs of the Society for Research in Child Development, 75, 4878.CrossRefGoogle ScholarPubMed
Lam, L. L., Emberly, E., Fraser, H. B., Neumann, S. M., Chen, E., Miller, G. E., et al. (2012). Factors underlying variable DNA methylation in a human community cohort. Proceedings of the National Academy of Sciences, 109(Suppl. 2), 1725317260.CrossRefGoogle Scholar
Lassalle, P., Molet, S., Janin, A., Van der Heyden, J., Tavernier, J., Fiers, W., et al. (1996). ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. Journal of Biological Chemistry, 271, 2045820464.CrossRefGoogle ScholarPubMed
Lee, K. W. K., Ku, S. K., Kim, S. W., & Bae, J. S. (2014). Endocan elicits severe vascular inflammatory responses in vitro and in vivo. Joural of Cellular Physiology, 229, 620630.CrossRefGoogle ScholarPubMed
Lee, K. W. K., Richmond, R., Hu, P., French, L., Shin, J., Bourdon, C., et al. (2015). Prenatal exposure to maternal cigarette smoking and DNA methylation: Epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age. Environmental Health Perspectives, 23, 193199.Google Scholar
Lewis, M. H., Gluck, J. P., Petitto, J. M., Hensley, L. L., & Ozer, H. (2000). Early social deprivation in nonhuman primates: Long-term effects on survival and cell-mediated immunity. Biological Psychiatry, 47, 119126.CrossRefGoogle ScholarPubMed
Liu, Y., Aryee, M. J., Padyukov, L., Fallin, M. D., Hesselberg, E., Runarsson, A., et al. (2013). Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nature Biotechnology, 31, 142147.CrossRefGoogle ScholarPubMed
Loman, M. M., Johnson, A. E., Westerlund, A., Pollak, S. D., Nelson, C. A., & Gunnar, M. R. (2013). The effect of early deprivation on executive attention in middle childhood. Journal of Child Psychology and Psychiatry, 54, 3745.CrossRefGoogle ScholarPubMed
Loman, M. M., Wiik, K. L., Frenn, K. A., Pollak, S. D., & Gunnar, M. R. (2009). Post-institutionalized children's development: Growth, cognitive, and language outcomes. Developmental and Behavioral Pediatrics, 30, 426434.CrossRefGoogle Scholar
Lubach, G. R., Coe, C. L., & Ershler, W. B. (1995). Effects of early rearing environment on immune responses of infant rhesus monkeys. Brain, Behavior and Immunity, 9, 3146.CrossRefGoogle ScholarPubMed
Luo, X., Zhang, Y., Ruan, X., Jiang, X., Zhu, L., Wang, X., et al. (2011). Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis. Diabetes, 60, 14351445.CrossRefGoogle ScholarPubMed
Lutz, P. E., & Turecki, G. (2014). DNA methylation and childhood maltreatment: From animal models to human studies. Journal of Neuroscience, 264, 142156.CrossRefGoogle ScholarPubMed
Maksimovic, J., Gordon, L., & Oshlack, A. (2012). SWAN: Subset-quantile within array normalization for illumina infinium HumanMethylation450 BeadChips. Genome Biology, 13, R44.CrossRefGoogle ScholarPubMed
Malnic, B., Godfrey, P. A., & Buck, L. B. (2004). The human olfactory receptor gene family. Proceedings of the National Academy of Sciences, 101, 25842589.CrossRefGoogle ScholarPubMed
Markunas, C. A., Xu, Z., Harlid, S., Wade, P. A., Lie, R. T., Taylor, J. A., et al. (2014). Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy. Environmental Health Perspectives, 122, 11471153.Google ScholarPubMed
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342348.CrossRefGoogle ScholarPubMed
McGuinness, D., McGlynn, L. M., Johnson, P. C., MacIntyre, A., Batty, G. D., Burns, H., et al. (2012). Socio-economic status is associated with epigenetic differences in the pSoBid cohort. International Journal of Epidemiology, 41, 151160.CrossRefGoogle ScholarPubMed
McKeown, C. R., Nowak, R. B., Gokhin, D. S., & Fowler, V. M. (2014). Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo. Developmental Dynamics, 243, 800817.CrossRefGoogle ScholarPubMed
Meaney, M. J., & Szyf, M. (2005). Environmental programming of stress responses through DNA methylation: Life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience, 7, 103123.Google Scholar
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., et al. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 110, 83028307.CrossRefGoogle ScholarPubMed
Mehta, M. A., Golembo, N. I., Nosarti, C., Colvert, E., Mota, A., Williams, S. C., et al. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: The English and Romanian Adoptees study pilot. Journal of Child Psychology and Psychiatry, 50, 943951.CrossRefGoogle ScholarPubMed
Melkonyan, H. S., Chang, W. C., Shapiro, J. P., Mahadevappa, M., Fitzpatrick, P. A., Kiefer, M. C., et al. (1997). SARPs: A family of secreted apoptosis-related proteins. Proceedings of the National Academy of Sciences, 94, 1363613641.CrossRefGoogle ScholarPubMed
Merico, D., Isserlin, R., Stueker, O., Emili, A., & Bader, G. D. (2010). Enrichment map: A network-based method for gene-set enrichment visualization and interpretation. PLOS ONE, 5, e13984.CrossRefGoogle ScholarPubMed
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., et al. (2009). Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proceedings of the National Academy of Sciences, 25, 1471614721.CrossRefGoogle Scholar
Moffitt, T. E., & Tank, K.-G. T. (2013). Childhood exposure to violence and lifelong health: Clinical intervention science and stress-biology research join forces. Development and Psychopathology, 25, 16191634.CrossRefGoogle ScholarPubMed
Monick, M. M., Beach, S. R. H., Plume, J., Sears, R., Gerrard, M., Brody, G. H., et al. (2012). Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. American Journal of Medical Genetics, 159B, 141151.CrossRefGoogle ScholarPubMed
Naumova, O. Y., Lee, M., Koposov, R., Szyf, M., Dozier, M., & Grigorenko, E. L. (2011). Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Development and Psychopathology, 24, 143155. doi:10.1017/S0954579411000605 CrossRefGoogle ScholarPubMed
Nishi, M., Horii-Hayashi, N., & Sasagawa, T. (2014). Effects of early life adverse experiences on the brain: Implications from maternal separation models in rodents. Frontiers in Neuroscience, 8, 166.CrossRefGoogle Scholar
Novakovic, B., Ryan, J., Pereira, N., Boughton, B., Craig, J. M., & Saffery, R. (2014). Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy. Epigenetics, 9, 377386.CrossRefGoogle ScholarPubMed
Pérez-de-Heredia, F., Gómez-Martínez, S., Díaz, L. E., Veses, A. M., Nova, E., Wärnberg, J., et al. (2015). Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—The HELENA study. European Journal of Pediatrics. Advance online publication.CrossRefGoogle ScholarPubMed
Perry, A. S., O'Hurley, G., Raheem, O. A., Brennan, K., Wong, S., O'Grady, A., et al. (2013). Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. International Journal of Cancer, 132, 17711780.CrossRefGoogle ScholarPubMed
Pickard, B. S., Malloy, M. P., Clark, L., Lehellard, S., Ewald, H. L., Mors, O., et al. (2005). Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18. Psychiatric Genetics, 15, 3744.CrossRefGoogle ScholarPubMed
Price, M. E., Cotton, A. M., Lam, L. L., Farré, P., Emberly, E., Brown, C. J., et al. (2013). Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array. Epigenetics Chromatin, 6, 4.CrossRefGoogle ScholarPubMed
Richmond, R. C., Simpkin, A. J., Woodward, G., Gaunt, T. R., Lyttleton, O., McArdle, W. L., et al. (2015). Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Human Molecular Genetics, 24, 22012217.CrossRefGoogle Scholar
Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., et al. (1989). Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science, 245, 10661073.CrossRefGoogle Scholar
Romano, E., Babchishin, L., Marquis, R., & Fréchette, S. (2014). Childhood maltreatment and educational outcomes. Trauma, Violence and Abuse. Advance online publication.Google ScholarPubMed
Saito, T., Mitomi, H., Imamhasan, A., Hayashi, T., Mitani, K., Takahashi, M., et al. (2014). Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma. Virchows Archives, 464, 135143.CrossRefGoogle ScholarPubMed
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., et al. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13, 24982504.CrossRefGoogle ScholarPubMed
Shenker, N. S., Polidoro, S., van Veldhoven, K., Sacerdote, C., Ricceri, F., Birrell, M. A., et al. (2013). Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Human Molecular Genetics, 22, 843851.CrossRefGoogle ScholarPubMed
Sheridan, M. A., Fox, N. A., Zeanah, C., McLaughlin, K. A., & Nelson, C. A. (2012). Variation in neural development as a result of exposure to institutionalization early in childhood. Proceedings of the National Academy of Sciences, 109, 1292712932.CrossRefGoogle ScholarPubMed
Shirtcliff, E. A., Coe, C. L., & Pollak, S. D. (2009). Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1. Proceedings of the National Academy of Sciences, 106, 29632967.CrossRefGoogle Scholar
Shonkoff, J., Boyce, W. T., & McEwen, B. S. (2009). Neuroscience, molecular biology, and the childhood roots of health disparities: Building a new framework for health promotion and disease prevention. Journal of the American Medical Association, 301, 22522259.CrossRefGoogle ScholarPubMed
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., et al. (2015). DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. American Journal of Medical Genetics, 168B, 3644.CrossRefGoogle Scholar
Smyth, G. K. (2005). Limma: Linear models for microarray data. In Gentleman, R., Carey, V. J., Huber, W., Irizarry, R. A., & Dudoit, S. (Eds.), Bioinformatics and computational biology solutions using R and Bioconductor (pp. 397420). New York: Springer–Verlag.CrossRefGoogle Scholar
Stefanski, V., & Engler, H. (1998). Effects of acute and chronic social stress on blood cellular immunity in rats. Physiology & Behavior, 64, 733741.CrossRefGoogle ScholarPubMed
Storey, J. D. (2003). The positive false discovery rate: A Bayesian interpretation and the q-value. Annals of Statistics, 31, 20132035.CrossRefGoogle Scholar
Stovall, K. C., & Dozier, M. (2000). The development of attachment in new relationships: Single subject analyses for 10 foster infants. Development and Psychopathology, 12, 133156.CrossRefGoogle ScholarPubMed
Sun, Y. V., Smith, A. K., Conneely, K. N., Chang, Q., Li, W., Lazarus, A., et al. (2013). Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Human Genetics, 132, 10271037.CrossRefGoogle ScholarPubMed
R Development Core Team. (2008). R: A language and environment for statistical computing. Vienna: Author.Google ScholarPubMed
Teh, A. L., Pan, H., Chen, L., Ong, M. L., Dogra, S. Wong, J., et al. (2014) The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Research, 24, 10641074.CrossRefGoogle ScholarPubMed
Tottenham, N., Hare, T. A., Quinn, B. T., McCarry, K., Nurse, M., Gilhooly, T., et al. (2010). Prolonged institutional rearing is associated with atypically larger amygdala volume and difficulties in emotion regulation. Developmental Science, 13, 4661.CrossRefGoogle ScholarPubMed
Tsaprouni, L. G., Yang, T.-P., Bell, J., Dick, K. J., Kanoni, S., Nisbet, J., et al. (2014). Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics, 9, 13821396.CrossRefGoogle ScholarPubMed
Vanderwert, R. E., Marshall, P. J., Nelson, C. A., Zeanah, C. H., & Fox, N. A. (2010). Timing of intervention affects brain electrical activity in children exposed to severe psychosocial neglect. PLOS ONE, 5, e11415.CrossRefGoogle Scholar
Wagner, J. R., Busche, S., Ge, B., Kwan, T., Pastinen, T., & Blanchette, M. (2014). The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts. Genome Biology, 15, R37.CrossRefGoogle ScholarPubMed
Waluk, D. P., Schultz, N., & Hunt, M. C. (2010). Identification of glycine N-acyltransferase-like 2 (GLYATL2) as a transferase that produces N-acyl glycines in humans. Journal of the American Federation of Societies of Experimental Biology, 24, 27952803.CrossRefGoogle ScholarPubMed
Waluk, D. P., Sucharski, F., Sipos, L., Silberring, J., & Hunt, M. C. (2012). Reversible lysine acetylation regulates activity of human glycine N-acyltransferase-like 2 (hGLYATL2): Implications for production of glycine-conjugated signaling molecules. Journal of Biological Chemistry, 287, 1615816167.CrossRefGoogle Scholar
Wang, G., He, Q., Feng, C., Liu, Y., Deng, Z., Qi, X., et al. (2014). The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism. Journal of Biological Chemistry, 289, 2792–2736.Google Scholar
Weber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M., et al. (2007). Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nature Genetics, 39, 457466.CrossRefGoogle Scholar
Zeanah, C. H., Gunnar, M. R., McCall, R. B., Kreppner, J. M., & Fox, N. A. (2011). Sensitive periods. Monographs of the Society for Research in Child Development, 74, 147162.CrossRefGoogle Scholar
Zeanah, C. H., Nelson, C. A., Fox, N. A., Smyke, A. T., Marshall, P. M., Parker, S. W., et al. (2003). Designing research to study the effects of institutionalization on brain and behavioral development: The Bucharest Early Intervention Project. Development and Psychopathology, 15, 885907.CrossRefGoogle ScholarPubMed
Zhang, Y., Xu, D., Huang, H., Chen, S., Wang, L., Zhu, L., et al. (2014). Regulation of glucose homeostasis and lipid metabolism by PPP1R3G-mediated hepatic glycogenesis. Molecular Endocrinology, 28, 116126.CrossRefGoogle ScholarPubMed
41
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *