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Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma

Authors: Zoya Marinova, Andreas Maercker, Andreas Küffer, Mark D. Robinson, Tomasz K. Wojdacz, Susanne Walitza, Edna Grünblatt, Andrea Burri

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Childhood trauma is associated with increased vulnerability to mental and somatic disorders later in life. Epigenetic modifications such as DNA methylation are one potential mechanism through which such long-lasting impairments/consequences can be explained. The aim of the present study was to investigate whether childhood trauma is associated with long-term DNA methylation alterations in old age.

Methods

We assessed genome-wide DNA methylation profiles in a cohort of former indentured child laborers (“Verdingkinder”) who suffered severe childhood adversities (N = 30; M age = 75.9 years), and compared them to control group with similar demographic characteristics (N = 15, M age = 72.8 years). DNA was isolated from epithelial buccal cells and hybridized to the Illumina Infinium 450 k DNA methylation array, which provides coverage of 485,000 methylation sites.

Results

After accounting for batch effects, age, gender and multiple testing, 71 differentially methylated CpG positions were identified between the two groups. They were annotated among others to genes involved in neuronal projections and neuronal development. Some of the identified genes with differential methylation (DLG associated protein 2, mechanistic target of rapamycin) have previously been associated with traumatic stress.

Conclusions

The results indicate specific epigenetic alterations in elderly individuals who were subjected to childhood adversities. Psychiatric and somatic comorbidities as well as differences in buccal epithelial cells proportion may contribute to the observed epigenetic differences.
Appendix
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Literature
1.
go back to reference Boyce P, Harris A. Childhood adversity, trauma and abuse: context and consequences. Aust N Z J of Psychiatry. 2011;45:608–10.CrossRef Boyce P, Harris A. Childhood adversity, trauma and abuse: context and consequences. Aust N Z J of Psychiatry. 2011;45:608–10.CrossRef
2.
go back to reference Kessler RC, McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Aguilar-Gaxiola S, Alhamzawi AO, Alonso J, Angermeyer M, Benjet C, Bromet E, Chatterji S, de Girolamo G, Demyttenaere K, Fayyad J, Florescu S, Gal G, Gureje O, Haro JM, Hu CY, Karam EG, Kawakami N, Lee S, Lépine JP, Ormel J, Posada-Villa J, Sagar R, Tsang A, Ustün TB, Vassilev S, Viana MC, Williams DR. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010;197:378–85.CrossRefPubMedPubMedCentral Kessler RC, McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Aguilar-Gaxiola S, Alhamzawi AO, Alonso J, Angermeyer M, Benjet C, Bromet E, Chatterji S, de Girolamo G, Demyttenaere K, Fayyad J, Florescu S, Gal G, Gureje O, Haro JM, Hu CY, Karam EG, Kawakami N, Lee S, Lépine JP, Ormel J, Posada-Villa J, Sagar R, Tsang A, Ustün TB, Vassilev S, Viana MC, Williams DR. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010;197:378–85.CrossRefPubMedPubMedCentral
3.
go back to reference Cuijpers P, Smit F, Unger F, Stikkelbroek Y, ten Have M, de Graaf R. The disease burden of childhood adversities in adults: a population-based study. Child Abuse Negl. 2011;35:937–45.CrossRefPubMed Cuijpers P, Smit F, Unger F, Stikkelbroek Y, ten Have M, de Graaf R. The disease burden of childhood adversities in adults: a population-based study. Child Abuse Negl. 2011;35:937–45.CrossRefPubMed
4.
go back to reference Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:113–23.CrossRefPubMedPubMedCentral Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:113–23.CrossRefPubMedPubMedCentral
5.
go back to reference McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:124–32.CrossRefPubMedPubMedCentral McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:124–32.CrossRefPubMedPubMedCentral
6.
go back to reference Ehlert U. Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology. 2013;38:1850–7.CrossRefPubMed Ehlert U. Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology. 2013;38:1850–7.CrossRefPubMed
7.
go back to reference Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89–97.CrossRefPubMed Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89–97.CrossRefPubMed
8.
go back to reference Labonté B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, Bureau A, Mechawar N, Szyf M, Meaney MJ, Turecki G. Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry. 2012;69:722–31.CrossRefPubMedPubMedCentral Labonté B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, Bureau A, Mechawar N, Szyf M, Meaney MJ, Turecki G. Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry. 2012;69:722–31.CrossRefPubMedPubMedCentral
9.
go back to reference Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW, Rex-Haffner M, Loeschner A, Gonik M, Mercer KB, Bradley B, Müller-Myhsok B, Ressler KJ, Binder EB. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci U S A. 2013;110:8302–7.CrossRefPubMedPubMedCentral Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW, Rex-Haffner M, Loeschner A, Gonik M, Mercer KB, Bradley B, Müller-Myhsok B, Ressler KJ, Binder EB. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci U S A. 2013;110:8302–7.CrossRefPubMedPubMedCentral
10.
go back to reference Suderman M, Borghol N, Pappas JJ, Pinto Pereira SM, Pembrey M, Hertzman C, Power C, Szyf M. Childhood abuse is associated with methylation of multiple loci in adult DNA. BMC Med Genomics. 2014;7:13.CrossRefPubMedPubMedCentral Suderman M, Borghol N, Pappas JJ, Pinto Pereira SM, Pembrey M, Hertzman C, Power C, Szyf M. Childhood abuse is associated with methylation of multiple loci in adult DNA. BMC Med Genomics. 2014;7:13.CrossRefPubMedPubMedCentral
11.
go back to reference Yang BZ, Zhang H, Ge W, Weder N, Douglas-Palumberi H, Perepletchikova F, Gelernter J, Kaufman J. Child abuse and epigenetic mechanisms of disease risk. Am J Prev Med. 2013;44:101–7.CrossRefPubMedPubMedCentral Yang BZ, Zhang H, Ge W, Weder N, Douglas-Palumberi H, Perepletchikova F, Gelernter J, Kaufman J. Child abuse and epigenetic mechanisms of disease risk. Am J Prev Med. 2013;44:101–7.CrossRefPubMedPubMedCentral
12.
go back to reference Naumova OY, Lee M, Koposov R, Szyf M, Dozier M, Grigorenko EL. Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Dev Psychopathol. 2012;24:143–55.CrossRefPubMed Naumova OY, Lee M, Koposov R, Szyf M, Dozier M, Grigorenko EL. Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Dev Psychopathol. 2012;24:143–55.CrossRefPubMed
13.
go back to reference Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B, Tang Y, Gillespie CF, Cubells JF, Ressler KJ. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B. 2011;156:700–8.CrossRef Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B, Tang Y, Gillespie CF, Cubells JF, Ressler KJ. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B. 2011;156:700–8.CrossRef
14.
go back to reference Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, Slieker RC, Stok AP, Thijssen PE, Müller F, van Zwet EW, Bock C, Meissner A, Lumey LH, Eline Slagboom P, Heijmans BT. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014;5:5592.CrossRefPubMedPubMedCentral Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, Slieker RC, Stok AP, Thijssen PE, Müller F, van Zwet EW, Bock C, Meissner A, Lumey LH, Eline Slagboom P, Heijmans BT. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014;5:5592.CrossRefPubMedPubMedCentral
15.
go back to reference Khulan B, Manning JR, Dunbar DR, Seckl JR, Raikkonen K, Eriksson JG, Drake AJ. Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state. Transl Psychiatry. 2014;4:e448.CrossRefPubMedPubMedCentral Khulan B, Manning JR, Dunbar DR, Seckl JR, Raikkonen K, Eriksson JG, Drake AJ. Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state. Transl Psychiatry. 2014;4:e448.CrossRefPubMedPubMedCentral
16.
go back to reference Leuenberger M. Versorgt und vergessen: Ehemalige Verdingkinder erzählen. Zurich: Rotpunktverlag. 2008. Leuenberger M. Versorgt und vergessen: Ehemalige Verdingkinder erzählen. Zurich: Rotpunktverlag. 2008.
17.
go back to reference Wohlwend L, Honeggerm A. Gestohlene Seelen: Verdingkinder in der Schweiz. Frauenfeld: Huber; 2004. Wohlwend L, Honeggerm A. Gestohlene Seelen: Verdingkinder in der Schweiz. Frauenfeld: Huber; 2004.
18.
go back to reference Burri A, Maercker A, Krammer S, Simmen-Janevska K. Childhood trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indentured child laborers in old age. PLoS One. 2013;8:e57826.CrossRefPubMedPubMedCentral Burri A, Maercker A, Krammer S, Simmen-Janevska K. Childhood trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indentured child laborers in old age. PLoS One. 2013;8:e57826.CrossRefPubMedPubMedCentral
19.
go back to reference Kuhlman KR, Maercker A, Bachem R, Simmen K, Burri A. Developmental and contextual factors in the role of severe childhood trauma in geriatric depression: the sample case of former indentured child laborers. Child Abuse Negl. 2013;37:969–78.CrossRefPubMed Kuhlman KR, Maercker A, Bachem R, Simmen K, Burri A. Developmental and contextual factors in the role of severe childhood trauma in geriatric depression: the sample case of former indentured child laborers. Child Abuse Negl. 2013;37:969–78.CrossRefPubMed
20.
go back to reference Maercker A, Hilpert P, Burri A. Childhood trauma and resilience in old age: applying a context model of resilience to a sample of former indentured child laborers. Aging Ment Health. 2016;20:616–26.CrossRefPubMed Maercker A, Hilpert P, Burri A. Childhood trauma and resilience in old age: applying a context model of resilience to a sample of former indentured child laborers. Aging Ment Health. 2016;20:616–26.CrossRefPubMed
21.
go back to reference Bernstein DP, Fink L. Childhood trauma questionnaire: a retrospective self-report manual. San Antonio: Harcourt Brace & Company; 1998. Bernstein DP, Fink L. Childhood trauma questionnaire: a retrospective self-report manual. San Antonio: Harcourt Brace & Company; 1998.
22.
go back to reference Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the childhood trauma questionnaire. Child Abuse Negl. 2003;27:169–90.CrossRefPubMed Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the childhood trauma questionnaire. Child Abuse Negl. 2003;27:169–90.CrossRefPubMed
23.
go back to reference Karos K, Niederstrasser N, Abidi L, Bernstein DP, Bader K. Factor structure, reliability, and known groups validity of the German version of the Childhood Trauma Questionnaire (Short-form) in Swiss patients and nonpatients. J Child Sex Abus. 2014;23:418–30.CrossRefPubMed Karos K, Niederstrasser N, Abidi L, Bernstein DP, Bader K. Factor structure, reliability, and known groups validity of the German version of the Childhood Trauma Questionnaire (Short-form) in Swiss patients and nonpatients. J Child Sex Abus. 2014;23:418–30.CrossRefPubMed
24.
go back to reference Martino D, Loke YJ, Gordon L, Ollikainen M, Cruickshank MN, Saffery R, Craig JM. Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance. Genome Biol. 2013;14:R42.CrossRefPubMedPubMedCentral Martino D, Loke YJ, Gordon L, Ollikainen M, Cruickshank MN, Saffery R, Craig JM. Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance. Genome Biol. 2013;14:R42.CrossRefPubMedPubMedCentral
25.
go back to reference Jones MJ, Farré P, McEwen LM, Macisaac JL, Watt K, Neumann SM, Emberly E, Cynader MS, Virji-Babul N, Kobor MS. Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in Down syndrome. BMC Med Genet. 2013;6:58. Jones MJ, Farré P, McEwen LM, Macisaac JL, Watt K, Neumann SM, Emberly E, Cynader MS, Virji-Babul N, Kobor MS. Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in Down syndrome. BMC Med Genet. 2013;6:58.
26.
go back to reference Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL, Fan JB, Shen R. High density DNA methylation array with single CpG site resolution. Genomics. 2011;98:288–95.CrossRefPubMed Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL, Fan JB, Shen R. High density DNA methylation array with single CpG site resolution. Genomics. 2011;98:288–95.CrossRefPubMed
27.
go back to reference R_Development_Core_Team. R. A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2013. R_Development_Core_Team. R. A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2013.
28.
go back to reference Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80.CrossRefPubMedPubMedCentral Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80.CrossRefPubMedPubMedCentral
29.
go back to reference Hansen KD, Ayree M, Irizary RA, Jaffe AE, Maksimovic J, Houseman A, Fortin JP, Triche T. Package “minfi”: Analyze Illumina’s 450 k methylation arrays. R package version 1.10.2. 2014. Hansen KD, Ayree M, Irizary RA, Jaffe AE, Maksimovic J, Houseman A, Fortin JP, Triche T. Package “minfi”: Analyze Illumina’s 450 k methylation arrays. R package version 1.10.2. 2014.
30.
go back to reference Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–9.CrossRefPubMedPubMedCentral Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–9.CrossRefPubMedPubMedCentral
31.
go back to reference Barfield RT, Kilaru V, Smith AK, Conneely KN. CpGassoc: an R function for analysis of DNA methylation microarray data. Bioinformatics. 2012;28:1280–1.CrossRefPubMedPubMedCentral Barfield RT, Kilaru V, Smith AK, Conneely KN. CpGassoc: an R function for analysis of DNA methylation microarray data. Bioinformatics. 2012;28:1280–1.CrossRefPubMedPubMedCentral
32.
go back to reference Eipel M, Mayer F, Arent T, Ferreira MR, Birkhofer C, Gerstenmaier U, Costa IG, Ritz-Timme S, Wagner W. Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures. Aging (Albany NY). 2016;8:1034–48.CrossRef Eipel M, Mayer F, Arent T, Ferreira MR, Birkhofer C, Gerstenmaier U, Costa IG, Ritz-Timme S, Wagner W. Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures. Aging (Albany NY). 2016;8:1034–48.CrossRef
33.
go back to reference Du P, Zhang X, Huang CC, Jafari N, Kibbe WA, Hou L, Lin SM. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinf. 2010;11:587.CrossRef Du P, Zhang X, Huang CC, Jafari N, Kibbe WA, Hou L, Lin SM. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinf. 2010;11:587.CrossRef
34.
go back to reference da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.CrossRef da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.CrossRef
35.
go back to reference Chen J, Bardes EE, Aronow BJ, Jegga AG. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009;37:W305–11.CrossRefPubMedPubMedCentral Chen J, Bardes EE, Aronow BJ, Jegga AG. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009;37:W305–11.CrossRefPubMedPubMedCentral
36.
go back to reference Nikitin A, Egorov S, Daraselia N, Mazo I. Pathway studio-the analysis and navigation of molecular networks. Bioinformatics. 2003;19:2155–7.CrossRefPubMed Nikitin A, Egorov S, Daraselia N, Mazo I. Pathway studio-the analysis and navigation of molecular networks. Bioinformatics. 2003;19:2155–7.CrossRefPubMed
37.
go back to reference Philibert R, Hollenbeck N, Andersen E, Osborn T, Gerrard M, Gibbons FX, Wang K. A quantitative epigenetic approach for the assessment of cigarette consumption. Front Psychol. 2015;6:656.CrossRefPubMedPubMedCentral Philibert R, Hollenbeck N, Andersen E, Osborn T, Gerrard M, Gibbons FX, Wang K. A quantitative epigenetic approach for the assessment of cigarette consumption. Front Psychol. 2015;6:656.CrossRefPubMedPubMedCentral
38.
go back to reference Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T. RA70 is a src kinase-associated protein expressed ubiquitously. Biochem Biophys Res Commun. 1998;252:738–42.CrossRefPubMed Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T. RA70 is a src kinase-associated protein expressed ubiquitously. Biochem Biophys Res Commun. 1998;252:738–42.CrossRefPubMed
39.
go back to reference Marie-Cardine A, Verhagen AM, Eckerskorn C, Schraven B. SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55. FEBS Lett. 1998;435:55–60.CrossRefPubMed Marie-Cardine A, Verhagen AM, Eckerskorn C, Schraven B. SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55. FEBS Lett. 1998;435:55–60.CrossRefPubMed
40.
go back to reference Shimamura S, Sasaki K, Tanaka M. The Src substrate SKAP2 regulates actin assembly by interacting with WAVE2 and cortactin proteins. J Biol Chem. 2013;288:1171–83.CrossRefPubMed Shimamura S, Sasaki K, Tanaka M. The Src substrate SKAP2 regulates actin assembly by interacting with WAVE2 and cortactin proteins. J Biol Chem. 2013;288:1171–83.CrossRefPubMed
41.
go back to reference Takahashi T, Yamashita H, Nagano Y, et al. Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. J Biol Chem. 2003;278:42225–33.CrossRefPubMed Takahashi T, Yamashita H, Nagano Y, et al. Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. J Biol Chem. 2003;278:42225–33.CrossRefPubMed
42.
43.
go back to reference Ball MP, Li JB, Gao Y, Lee JH, LeProust EM, Park IH, Xie B, Daley GQ, GM C. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27:361–8.CrossRefPubMedPubMedCentral Ball MP, Li JB, Gao Y, Lee JH, LeProust EM, Park IH, Xie B, Daley GQ, GM C. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27:361–8.CrossRefPubMedPubMedCentral
44.
go back to reference Lou S, Lee HM, Qin H, Li JW, Gao Z, Liu X, Chan LL, Kl Lam V, So WY, Wang Y, Lok S, Wang J, Ma RC, Tsui SK, Chan JC, Chan TF, Yip KY. Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation. Genome Biol. 2014;15:408.CrossRefPubMedPubMedCentral Lou S, Lee HM, Qin H, Li JW, Gao Z, Liu X, Chan LL, Kl Lam V, So WY, Wang Y, Lok S, Wang J, Ma RC, Tsui SK, Chan JC, Chan TF, Yip KY. Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation. Genome Biol. 2014;15:408.CrossRefPubMedPubMedCentral
45.
go back to reference Chertkow-Deutsher Y, Cohen H, Klein E, Ben-Shachar D. DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2. Int J Neuropsychopharmacol. 2010;13:347–59.CrossRefPubMed Chertkow-Deutsher Y, Cohen H, Klein E, Ben-Shachar D. DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2. Int J Neuropsychopharmacol. 2010;13:347–59.CrossRefPubMed
46.
go back to reference Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008;90:28–35.CrossRefPubMedPubMedCentral Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008;90:28–35.CrossRefPubMedPubMedCentral
47.
go back to reference Sui ZX, Liu H, Wang HT, Yang ZL, Liu JG, Xu AJ, Lu HX. Alteration of apoptosis and Akt/mTOR signal pathway in hippocampal neurons of rat with post-traumatic stress. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014;45:221–4.PubMed Sui ZX, Liu H, Wang HT, Yang ZL, Liu JG, Xu AJ, Lu HX. Alteration of apoptosis and Akt/mTOR signal pathway in hippocampal neurons of rat with post-traumatic stress. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014;45:221–4.PubMed
48.
go back to reference Murgatroyd C, Wu Y, Bockmühl Y, Spengler D. The Janus face of DNA methylation in aging. Aging (Albany NY). 2010;2:107–10.CrossRef Murgatroyd C, Wu Y, Bockmühl Y, Spengler D. The Janus face of DNA methylation in aging. Aging (Albany NY). 2010;2:107–10.CrossRef
49.
go back to reference Boks MP, van Mierlo HC, Rutten BP, Radstake TR, De Witte L, Geuze E, Horvath S, Schalkwyk LC, Vinkers CH, Broen JC, Vermetten E. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder. Psychoneuroendocrinology. 2015;51:506–12.CrossRefPubMed Boks MP, van Mierlo HC, Rutten BP, Radstake TR, De Witte L, Geuze E, Horvath S, Schalkwyk LC, Vinkers CH, Broen JC, Vermetten E. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder. Psychoneuroendocrinology. 2015;51:506–12.CrossRefPubMed
50.
go back to reference Hodges E, Molaro A, Dos Santos CO, Thekkat P, Song Q, Uren PJ, Park J, Butler J, Rafii S, McCombie WR, Smith AD, Hannon GJ. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Mol Cell. 2011;44:17–28.CrossRefPubMedPubMedCentral Hodges E, Molaro A, Dos Santos CO, Thekkat P, Song Q, Uren PJ, Park J, Butler J, Rafii S, McCombie WR, Smith AD, Hannon GJ. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Mol Cell. 2011;44:17–28.CrossRefPubMedPubMedCentral
51.
go back to reference Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev. 2013;84:49–57.CrossRefPubMed Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev. 2013;84:49–57.CrossRefPubMed
Metadata
Title
DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma
Authors
Zoya Marinova
Andreas Maercker
Andreas Küffer
Mark D. Robinson
Tomasz K. Wojdacz
Susanne Walitza
Edna Grünblatt
Andrea Burri
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0370-2

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