DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample

Radhika Kandaswamy; Eilis Hannon; Louise Arseneault; Georgina Mansell; Karen Sugden; Benjamin Williams; Joe Burrage; James R Staley; Ehsan Pishva; Aisha Dahir; Susanna Roberts; Andrea Danese; Jonathan Mill; Helen Fisher; Chloe Wong

doi:10.1080/15592294.2020.1853317

DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample

Radhika Kandaswamy, Eilis Hannon, Louise Arseneault, Georgina Mansell, Karen Sugden, Benjamin Williams, Joe Burrage, James R Staley, Ehsan Pishva, Aisha Dahir, Susanna Roberts, Andrea Danese, Jonathan Mill, Helen Fisher, Chloe Wong

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Abstract

Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P < 5e-05), with altered DNAm trajectories between ages 10–18 associated with severe adolescent victimization (∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (∆Beta range = −2.2%−3.4%) and 42 buccal (∆Beta range = −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in LGR6 and ANK3 (Šidák P = 5e-09 and 4.07e-06), and one upstream of CCL27 (Šidák P = 2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.

Original language	English
Pages (from-to)	1169-1186
Number of pages	18
Journal	Epigenetics
Volume	16
Issue number	11
Early online date	29 Dec 2020
DOIs	https://doi.org/10.1080/15592294.2020.1853317
Publication status	Published - 2 Nov 2021

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Kandaswamy, R., Hannon, E., Arseneault, L., Mansell, G., Sugden, K., Williams, B., Burrage, J., Staley, J. R., Pishva, E., Dahir, A., Roberts, S., Danese, A., Mill, J., Fisher, H., & Wong, C. (2021). DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample. Epigenetics, 16(11), 1169-1186. https://doi.org/10.1080/15592294.2020.1853317

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title = "DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample",

abstract = "Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P < 5e-05), with altered DNAm trajectories between ages 10–18 associated with severe adolescent victimization (∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (∆Beta range = −2.2%−3.4%) and 42 buccal (∆Beta range = −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in LGR6 and ANK3 ({\v S}id{\'a}k P = 5e-09 and 4.07e-06), and one upstream of CCL27 ({\v S}id{\'a}k P = 2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.",

author = "Radhika Kandaswamy and Eilis Hannon and Louise Arseneault and Georgina Mansell and Karen Sugden and Benjamin Williams and Joe Burrage and Staley, {James R} and Ehsan Pishva and Aisha Dahir and Susanna Roberts and Andrea Danese and Jonathan Mill and Helen Fisher and Chloe Wong",

note = "Funding Information: This work was supported by a joint grant from the Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council [ES/N000277/1]; HLF is supported by the ESRC Centre for Society and Mental Health [ES/S012567/1]; MQ: Transforming Mental Health Fellows Award to HLF [MQ14F40]; Medical Research Council grant to JRS [MR/M025020/1]; Medical Research Council [G1002190]; National Institute of Child Health and Human Development [HD077482]. We are grateful to the study mothers and fathers, the twins, and the twins? teachers for their participation. Our thanks to Professors Terrie Moffitt and Avshalom Caspi who founded the E-Risk study, members of the E-Risk team for their dedication, hard work, and insights, the Nuffield Foundation, the Avielle Foundation, and CACI, Inc. This work was supported by a joint UK Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council (BBSRC) grant [ES/N000277/1] to CCYW. The E-Risk Study is supported by the Medical Research Council [G1002190]. This work was also supported by the National Institute of Child Health and Human Development [HD077482], the Jacobs Foundation, and an MQ Fellows Award [MQ14F40] to HLF. AD is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King?s College London. JRS was supported by a grant from the Medical Research Council [MR/M025020/1]. LA is the Mental Health Leadership Fellow for the UK ESRC. HLF receives salary support from the ESRC Centre for Society and Mental Health at King?s College London [ES/S012567/1]. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health and Social Care, the ESRC or King?s College London. Funding Information: This work was supported by a joint UK Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council (BBSRC) grant [ES/N000277/1] to CCYW. The E-Risk Study is supported by the Medical Research Council [G1002190]. This work was also supported by the National Institute of Child Health and Human Development [HD077482], the Jacobs Foundation, and an MQ Fellows Award [MQ14F40] to HLF. AD is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. JRS was supported by a grant from the Medical Research Council [MR/M025020/1]. LA is the Mental Health Leadership Fellow for the UK ESRC. HLF receives salary support from the ESRC Centre for Society and Mental Health at King{\textquoteright}s College London [ES/S012567/1]. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health and Social Care, the ESRC or King{\textquoteright}s College London. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2021",

month = nov,

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doi = "10.1080/15592294.2020.1853317",

language = "English",

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Kandaswamy, R, Hannon, E, Arseneault, L, Mansell, G, Sugden, K, Williams, B, Burrage, J, Staley, JR, Pishva, E, Dahir, A, Roberts, S , Danese, A, Mill, J, Fisher, H & Wong, C 2021, 'DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample', Epigenetics, vol. 16, no. 11, pp. 1169-1186. https://doi.org/10.1080/15592294.2020.1853317

TY - JOUR

T1 - DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample

AU - Kandaswamy, Radhika

AU - Hannon, Eilis

AU - Arseneault, Louise

AU - Mansell, Georgina

AU - Sugden, Karen

AU - Williams, Benjamin

AU - Burrage, Joe

AU - Staley, James R

AU - Pishva, Ehsan

AU - Dahir, Aisha

AU - Roberts, Susanna

AU - Danese, Andrea

AU - Mill, Jonathan

AU - Fisher, Helen

AU - Wong, Chloe

N1 - Funding Information: This work was supported by a joint grant from the Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council [ES/N000277/1]; HLF is supported by the ESRC Centre for Society and Mental Health [ES/S012567/1]; MQ: Transforming Mental Health Fellows Award to HLF [MQ14F40]; Medical Research Council grant to JRS [MR/M025020/1]; Medical Research Council [G1002190]; National Institute of Child Health and Human Development [HD077482]. We are grateful to the study mothers and fathers, the twins, and the twins? teachers for their participation. Our thanks to Professors Terrie Moffitt and Avshalom Caspi who founded the E-Risk study, members of the E-Risk team for their dedication, hard work, and insights, the Nuffield Foundation, the Avielle Foundation, and CACI, Inc. This work was supported by a joint UK Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council (BBSRC) grant [ES/N000277/1] to CCYW. The E-Risk Study is supported by the Medical Research Council [G1002190]. This work was also supported by the National Institute of Child Health and Human Development [HD077482], the Jacobs Foundation, and an MQ Fellows Award [MQ14F40] to HLF. AD is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King?s College London. JRS was supported by a grant from the Medical Research Council [MR/M025020/1]. LA is the Mental Health Leadership Fellow for the UK ESRC. HLF receives salary support from the ESRC Centre for Society and Mental Health at King?s College London [ES/S012567/1]. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health and Social Care, the ESRC or King?s College London. Funding Information: This work was supported by a joint UK Economic and Social Research Council (ESRC) and Biotechnology and Biological Sciences Research Council (BBSRC) grant [ES/N000277/1] to CCYW. The E-Risk Study is supported by the Medical Research Council [G1002190]. This work was also supported by the National Institute of Child Health and Human Development [HD077482], the Jacobs Foundation, and an MQ Fellows Award [MQ14F40] to HLF. AD is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London. JRS was supported by a grant from the Medical Research Council [MR/M025020/1]. LA is the Mental Health Leadership Fellow for the UK ESRC. HLF receives salary support from the ESRC Centre for Society and Mental Health at King’s College London [ES/S012567/1]. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health and Social Care, the ESRC or King’s College London. Publisher Copyright: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2021/11/2

Y1 - 2021/11/2

N2 - Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P < 5e-05), with altered DNAm trajectories between ages 10–18 associated with severe adolescent victimization (∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (∆Beta range = −2.2%−3.4%) and 42 buccal (∆Beta range = −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in LGR6 and ANK3 (Šidák P = 5e-09 and 4.07e-06), and one upstream of CCL27 (Šidák P = 2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.

AB - Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P < 5e-05), with altered DNAm trajectories between ages 10–18 associated with severe adolescent victimization (∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (∆Beta range = −2.2%−3.4%) and 42 buccal (∆Beta range = −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in LGR6 and ANK3 (Šidák P = 5e-09 and 4.07e-06), and one upstream of CCL27 (Šidák P = 2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.

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U2 - 10.1080/15592294.2020.1853317

DO - 10.1080/15592294.2020.1853317

M3 - Article

SN - 1559-2294

VL - 16

SP - 1169

EP - 1186

JO - Epigenetics

JF - Epigenetics

IS - 11

ER -

DNA methylation signatures of adolescent victimization: Analysis of a longitudinal monozygotic twin sample

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