Association of Childhood Chronic Physical Aggression with a DNA Methylation Signature in Adult Human T Cells
Open accessAbstract
BACKGROUND: Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, CPA is associated with early childhood adverse environments and long-term negative consequences. Alterations in DNA methylation, a covalent modification of DNA that regulates genome function, have been associated with early childhood adversity. AIMS: To test the hypothesis that a trajectory of chronic physical aggression during childhood is associated with a distinct DNA methylation profile during adulthood. METHODS: We analyzed genome-wide promoter DNA methylation profiles of T cells from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Methylation profiles covering the promoter regions of 20 000 genes and 400 microRNAs were generated using MeDIP followed by hybridization to microarrays. RESULTS: In total, 448 distinct gene promoters were differentially methylated in CPA. Functionally, many of these genes have previously been shown to play a role in aggression and were enriched in biological pathways affected by behavior. Their locations in the genome tended to form clusters spanning millions of bases in the genome. CONCLUSIONS: This study provides evidence of clustered and genome-wide variation in promoter DNA methylation in young adults that associates with a history of chronic physical aggression from 6 to 15 years of age. However, longitudinal studies of methylation during early childhood will be necessary to determine if and how this methylation variation in T cells DNA plays a role in early development of chronic physical aggression.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
A genome-wide study of men found that parental physical aggression in childhood and adolescence was associated with differential methylation in genes previously implicated in aggressive behavior.
“A genome-wide study of men found that parental physical aggression in childhood and adolescence was associated with differential methylation in genes previously implicated in aggressive behavior [50].”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [50]
The Methods describe a genome-wide methylation study of adult men assessed for their own physical aggression from ages 6 to 15; the Discussion reports differential methylation in genes previously linked to aggression. The paper does not study parental physical aggression, so that part of the claim is unsupported. The indexed passages provide section labels but no page numbers. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThere were significant overrepresentations in chromosomes 4 and 5 (p = 0.01).
“Significant overrepresentations in chromosomes 4 and 5 (p = 0.01).”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Provençal [126]
The Results section (‘Methylation associated with chronic physical aggression clusters by genomic location’; page unavailable) reports a higher density of methylation differences on chromosomes 4 and 5. It does not report that the chromosome-wide overrepresentations were significant at p = 0.01; its separate finding of significant enrichment concerns six 500-kb regions. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe review found converging evidence for a role of AVPR1A in child aggression coming from genome-wide association, epigenomic, and candidate gene studies.
“Nonetheless, we found converging evidence for a role of AVPR1A in child aggression coming from genome-wide association [35], epigenomic [126], and candidate gene [101] studies.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [126]
Five genes previously linked with aggression were differentially methylated (AVPR1A, HTR1D, GRM5 less methylated in CPA group, DRD1, SLC6A3 more methylated in CPA group).
“Five genes previously linked with aggression were differentially methylated (AVPR1A, HTR1D, GRM5 less methylated in CPA group, DRD1, SLC6A3 more methylated in CPA group).”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Provençal [126]
448 distinct gene promoters were differentially methylated in CPA.
“448 distinct gene promoters differentially methylated in CPA.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Provençal [126]
Of these promoters, 277 were more methylated in the control group, and 171 were more methylated in the CPA group.
“Of these promoters, 277 more methylated in the control group, and 171 more methylated in the CPA group.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Provençal [126]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796 · see citing works
Role of genotype in the cycle of violence in maltreated children
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., Taylor, A., & Poulton, R. (2002) · Science · doi:10.1126/science.1072290 · Cited by 4,842 · see citing works
CpG-rich islands and the function of DNA methylation
Bird, A. P. (1986) · Nature · doi:10.1038/321209a0 · Cited by 3,777 · see citing works
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531 · see citing works
Bioinformatics and Computational Biology Solutions Using R and Bioconductor
Gentleman, R. C., Carey, V. J., Huber, W. K., Irizarry, R. A., & Dudoit, S. (2005) · Statistics in the health sciences · doi:10.1007/0-387-29362-0 · Cited by 3,470 · see citing works
CpG islands in vertebrate genomes.
Gardiner-Garden, M., & Frommer, M. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90689-9 · Cited by 3,462 · see citing works
Persistent epigenetic differences associated with prenatal exposure to famine in humans
Heijmans, B. T., Tobi, E. W., Stein, A. D., Putter, H., Blauw, G. J., Susser, E. S., Slagboom, P. E., & Lumey, L. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806560105 · Cited by 3,082 · see citing works
Environmental epigenomics and disease susceptibility
Jirtle, R. L., & Skinner, M. K. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2045 · Cited by 2,492 · see citing works
Transposable elements: targets for early nutritional effects on epigenetic gene regulation
Waterland, R. A., & Jirtle, R. L. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5293-5300.2003 · Cited by 2,019 · cited 1× · see citing works
“There is a growing body of evidence suggesting that in addition to the innate endogenous processes sculpting the DNA methylation pattern during gestation, the DNA methylation pattern is responsive to external environmental exposures including the social environment during both intra-uterine development and after birth…”
BackgroundWeber, M., Davies, J. J., Wittig, D., Oakeley, E., Haase, M., Lam, W., & Schübeler, D. (2005) · Nature Genetics · doi:10.1038/ng1598 · Cited by 1,885 · see citing works
Broidy, L. M., Nagin, D. S., Tremblay, R. E., Bates, J. E., Brame, B., Dodge, K. A., Fergusson, D., Horwood, J. L., Loeber, R., Laird, R., et al. (2003) · Developmental Psychology · doi:10.1037//0012-1649.39.2.222 · Cited by 1,637 · see citing works
Self-citationAllele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3275 · Cited by 1,447 · see citing works
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008) · Epigenetics · doi:10.4161/epi.3.2.6034 · Cited by 1,432 · see citing works
Nagin, D. S., & Tremblay, R. E. (1999) · Child Development · doi:10.1111/1467-8624.00086 · Cited by 1,361 · see citing works
Self-citationBroidy, L. M., Nagin, D. S., Tremblay, R. E., et al. (2003) · Developmental Psychology · doi:10.1037/0012-1649.39.2.222 · Cited by 1,198 · see citing works
Self-citationDynamic DNA methylation programs persistent adverse effects of early-life stress
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmühl, Y., Fischer, D., Holsboer, F., Wotjak, C. T., Almeida, O. F. X., & Spengler, D. (2009) · Nature Neuroscience · doi:10.1038/nn.2436 · Cited by 1,162 · see citing works
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001851 · Cited by 1,158 · see citing works
Dolinoy, D. C., Weidman, J. R., Waterland, R. A., & Jirtle, R. L. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.8700 · Cited by 932 · see citing works
Sinclair, K. D., Allegrucci, C., Singh, R., Gardner, D. S., Sebastian, S., Bispham, J., Thurston, A., Huntley, J. F., Rees, W. D., Maloney, C. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707258104 · Cited by 812 · see citing works
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor
Ressler, K. J., Mercer, K. B., Bradley, B., Jovanovic, T., Mahan, A., Kerley, K., Norrholm, S. D., Kilaru, V., Smith, A. K., Myers, A. J., et al. (2011) · Nature · doi:10.1038/nature09856 · Cited by 800 · see citing works
CpG methylation, chromatin structure and gene silencing—a three‐way connection
Razin, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.4905 · Cited by 791 · see citing works
Early experience and serotonin transporter gene variation interact to influence primate CNS function
Bennett, A. J., Lesch, K., Heils, A., Long, J. C., Lorenz, J. G., Shoaf, S. E., Champoux, M. C., Suomi, S. J., Linnoila, M., & Higley, J. D. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000949 · Cited by 659 · see citing works
A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis
Down, T. A., Rakyan, V. K., Turner, D., Flicek, P., Li, H., Kulesha, E., Gräf, S., Johnson, N., Herrero, J., Tomazou, E. M., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1414 · Cited by 651 · see citing works
Côté, S., Vaillancourt, T., LeBlanc, J. C., Nagin, D. S., & Tremblay, R. E. (2006) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-005-9001-z · Cited by 641 · see citing works
Self-citationEpigenetic and immune function profiles associated with posttraumatic stress disorder
Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de los Santos, R., Goldmann, E., & Galea, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910794107 · Cited by 518 · see citing works
Evidence for an instructive mechanism of de novo methylation in cancer cells
Keshet, I., Schlesinger, Y., Farkash, S., Rand, E., Hecht, M., Segal, E., Pikarsky, E., Young, R. A., Niveleau, A., Cedar, H., et al. (2006) · Nature Genetics · doi:10.1038/ng1719 · Cited by 477 · see citing works
Tremblay, R. E. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02211.x · Cited by 462 · see citing works
Self-citationBroad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
McGowan, P. O., Suderman, M., Sasaki, A., Huang, T. C. T., Hallett, M., Meaney, M. J., & Szyf, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014739 · Cited by 452 · see citing works
Self-citationNagin, D. S., & Tremblay, R. E. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.4.389 · Cited by 449 · see citing works
Self-citationJin, S.-G., Kadam, S., & Pfeifer, G. P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq223 · Cited by 437 · see citing works
Comprehensive high-throughput arrays for relative methylation (CHARM)Preprint
Irizarry, R. A., Ladd‐Acosta, C., Carvalho, B. S., Wu, H., Brandenburg, S. A., Jeddeloh, J. A., Wen, B., & Feinberg, A. P. (2008) · Genome Research · doi:10.1101/gr.7301508 · Cited by 433 · see citing works
Nelson, R. J., & Chiavegatto, S. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01996-2 · Cited by 429 · see citing works
Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome
Guerrero‐Bosagna, C., Settles, M. L., Lucker, B. F., & Skinner, M. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013100 · Cited by 427 · see citing works
Alink, L. R. A., Mesman, J., van Zeijl, J., Stolk, M. N., Juffer, F., Koot, H. M., Bakermans‐Kranenburg, M. J., & van IJzendoorn, M. H. (2006) · Child Development · doi:10.1111/j.1467-8624.2006.00912.x · Cited by 420 · see citing works
Associations with early-life socio-economic position in adult DNA methylation
Borghol, N., Suderman, M. J., McArdle, W. L., Racine, A., Hallett, M. T., Pembrey, M. E., Hertzman, C., Power, C., & Moshe Szyf, A. (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyr147 · Cited by 415 · see citing works
Self-citationCampbell, S. B., Spieker, S., Burchinal, M., Poe, M. D., & The NICHD Early Child Care Research Network (2006) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2006.01636.x · Cited by 391 · see citing works
Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder
Smith, A. K., Conneely, K. N., Kilaru, V., Mercer, K. B., Weiss, T. E., Bradley, B., Tang, Y., Gillespie, C. F., Cubells, J. F., & Ressler, K. J. (2011) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31212 · Cited by 355 · see citing works
Weaver, I. C. G., Diorio, J. C., Seckl, J. R., Moshe Szyf, A., & Meaney, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1321.099 · Cited by 330 · see citing works
DNA methylation patterns Formation and function
Razin, A., & Moshe Szyf, A. (1984) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(84)90043-5 · Cited by 318 · see citing works
The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells
Provençal, N., Suderman, M. J., Guillemin, C., Massart, R., Ruggiero, A., Wang, D., Bennett, A. J., Pierre, P. J., Friedman, D. P., Côté, S. M., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1470-12.2012 · Cited by 312 · see citing works
Self-citationEscalated aggressive behavior: Dopamine, serotonin and GABA
de Almeida, R. M. M., Ferrari, P. F., Parmigiani, S., & Miczek, K. A. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.10.004 · Cited by 303 · see citing works
van IJzendoorn, M. H., Caspers, K., Bakermans-Kranenburg, M. J., Beach, S. R. H., & Philibert, R. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.008 · Cited by 264 · see citing works
Bell, C. G., Finer, S., Lindgren, C. M., Wilson, G. A., Rakyan, V. K., Teschendorff, A. E., Akan, P., Stupka, E., Down, T. A., Prokopenko, I., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014040 · Cited by 255 · see citing works
Pingault, J.-B., Tremblay, R. E., Vitaro, F., Carbonneau, R., Genolini, C., Falissard, B., & Côté, S. M. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10121732 · Cited by 244 · see citing works
Self-citationRossi, R. L., Rossetti, G., Wenandy, L., Curti, S., Ripamonti, A., Bonnal, R. J. P., Birolo, R. S., Moro, M., Crosti, M., Gruarin, P., et al. (2011) · Nature Immunology · doi:10.1038/ni.2057 · Cited by 242 · see citing works
The Epigenetic Landscape of Latent Kaposi Sarcoma-Associated Herpesvirus Genomes
Günther, T., & Grundhoff, A. T. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000935 · Cited by 242 · see citing works
Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation
Liu, Y., Balaraman, Y., Wang, G., Nephew, K. P., & Zhou, F. (2009) · Epigenetics · doi:10.4161/epi.4.7.9925 · Cited by 239 · see citing works
Physical aggression and expressive vocabulary in 19-month-old twins.
Dionne, G., Tremblay, R. E., Boivin, M., Laplante, D. P., & Pérusse, D. (2003) · Developmental Psychology · doi:10.1037//0012-1649.39.2.261 · Cited by 226 · see citing works
Self-citationMovassagh, M., Choy, M., Goddard, M. J., Bennett, M. R., Down, T. A., & Foo, R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008564 · Cited by 224 · see citing works
Guo, G., Roettger, M. E., & Shih, J. C. (2006) · Human Genetics · doi:10.1007/s00439-006-0244-8 · Cited by 220 · see citing works
MacLennan, N. K., James, S. J., Melnyk, S., Piroozi, A., Jernigan, S., Hsu, J. L., Janke, S. M., Pham, T. D., & Lane, R. H. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00042.2004 · Cited by 210 · see citing works
Nair, S. S., Coolen, M. W., Stirzaker, C., Song, J. Z., Statham, A. L., Strbenac, D., Robinson, M. D., & Clark, S. J. (2011) · Epigenetics · doi:10.4161/epi.6.1.13313 · Cited by 210 · see citing works
Predictive Validity and Early Predictors of Peer-Victimization Trajectories in Preschool
Barker, E. D., Boivin, M., Brendgen, M. R., Fontaine, N. M. G., Arseneault, L., Vitaro, F., Bissonnette, C., & Tremblay, R. E. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.10.1185 · Cited by 210 · see citing works
Self-citationWang, D., Szyf, M., Benkelfat, C., Provençal, N., Turecki, G., Caramaschi, D., Côté, S. M., Vitaro, F., Tremblay, R. E., & Booij, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039501 · Cited by 208 · see citing works
Self-citationDevelopmental Trajectories of Male Physical Violence and Theft
Barker, E. D., Séguin, J. R., WHITE, H. R., Bates, M. E., Lacourse, É., Carbonneau, R., & Tremblay, R. E. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.5.592 · Cited by 205 · see citing works
Self-citationSéguin, J. R., Boulerice, B., Harden, P. W., Tremblay, R. E., & Pihl, R. O. (1999) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00536 · Cited by 200 · see citing works
Self-citationMorris, M. R., Ricketts, C. J., Gentle, D., McRonald, F. E., Carli, N., Khalili, H. S., Brown, M. D., Kishida, T., Yao, M., Banks, R. E., et al. (2010) · Oncogene · doi:10.1038/onc.2010.525 · Cited by 195 · see citing works
Arsenio, W. F. (2004) · Cited by 186 · see citing works
Genetic determinants of aggression and impulsivity in humans
Pavlov, K. A., Chistiakov, D. A., & Chekhonin, V. P. (2012) · Journal of Applied Genetics · doi:10.1007/s13353-011-0069-6 · Cited by 184 · see citing works
Uddin, M., Koenen, K. C., Aiello, A. E., Wildman, D. E., de los Santos, R., & Galea, S. (2011) · Psychological Medicine · doi:10.1017/s0033291710001674 · Cited by 174 · see citing works
Dopamine Receptor Genetic Variation, Psychosis, and Aggression in Alzheimer Disease
Sweet, R. A., Nimgaonkar, V. L., Kamboh, M. I., López, O. L., Zhang, F., & DeKosky, S. T. (1998) · Archives of Neurology · doi:10.1001/archneur.55.10.1335 · Cited by 164 · see citing works
Szyf, M. (2011) · Epigenetics · doi:10.4161/epi.6.8.16793 · Cited by 161 · see citing works
Physical aggression and expressive vocabulary in 19-month-old twins.
Dionne, G., Tremblay, R. E., Boivin, M., et al. (2003) · Developmental Psychology · doi:10.1037/0012-1649.39.2.261 · Cited by 157 · see citing works
Self-citationWeaver, I. C. G., Plante, P. L., Weaver, S., Parent, A., Sharma, S., Diorio, J. C., Chapman, K. E., Seckl, J. R., Moshe Szyf, A., & Meaney, M. J. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00635-9 · Cited by 154 · see citing works
Côté, S. M., Boivin, M., Nagin, D. S., Japel, C., Xu, Q., Zoccolillo, M., Junger, M., & Tremblay, R. E. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.11.1305 · Cited by 154 · see citing works
Self-citationThe Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders
Siegel, A., Bhatt, S., Bhatt, R., & Zalcman, S. S. (2007) · Current Neuropharmacology · doi:10.2174/157015907780866929 · Cited by 145 · see citing works
Epigenetic status of the H19 locus in human oocytes following in vitro maturation
Borghol, N., Lornage, J., Blachère, T., et al. (2005) · Genomics · doi:10.1016/j.ygeno.2005.10.008 · Cited by 142 · see citing works
Epithelial Progeny of Estrogen-Exposed Breast Progenitor Cells Display a Cancer-like Methylome
Cheng, A. S. L., Culhane, A. C., Chan, M. W. Y., Venkataramu, C. R., Ehrich, M., Nasir, A., Rodriguez, B. A. T., Liu, J., Yan, P. S., Quackenbush, J. F., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5547 · Cited by 140 · see citing works
Ke, X., Lei, Q., James, S. J., Kelleher, S. L., Melnyk, S., Jernigan, S., Yu, X., Wang, L., Callaway, C. W., Gill, G., et al. (2005) · Physiological Genomics · doi:10.1152/physiolgenomics.00093.2005 · Cited by 136 · see citing works
Takeshima, H., Yamashita, S., Shimazu, T., Niwa, T., & Ushijima, T. (2009) · Genome Research · doi:10.1101/gr.093310.109 · Cited by 135 · see citing works
Robinson, M. D., Stirzaker, C., Statham, A. L., Coolen, M. W., Song, J. Z., Nair, S. S., Strbenac, D., Speed, T. P., & Clark, S. J. (2010) · Genome Research · doi:10.1101/gr.110601.110 · Cited by 131 · see citing works
van Lier, P. A. C., van der Ende, J., Koot, H. M., & Verhulst, F. C. (2007) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2006.01724.x · Cited by 130 · see citing works
The neurobiology of aggression and rage: Role of cytokines
Zalcman, S. S., & Siegel, A. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.05.002 · Cited by 129 · see citing works
Cheung, H., Lee, T., Davis, A., Taft, D. H., Rennert, O. M., & Chan, W. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605505 · Cited by 124 · see citing works
Behavioral and Pharmacogenetics of Aggressive Behavior
Takahashi, A., Quadros, I. M., de Almeida, R. M. M., & Miczek, K. A. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_191 · Cited by 120 · see citing works
Epigenetic control of the expression of a primate-specific microRNA cluster in human cancer cells
Tsai, K., Kao, H.-W., Chen, H., et al. (2009) · Epigenetics · doi:10.4161/epi.4.8.10230 · Cited by 115 · see citing works
Comparative methylome analysis of benign and malignant peripheral nerve sheath tumorsPreprint
Feber, A., Wilson, G. A., Zhang, L., Presneau, N., Idowu, B. D., Down, T. A., Rakyan, V. K., Noon, L. A., Lloyd, A. C., Stupka, E., et al. (2011) · Genome Research · doi:10.1101/gr.109678.110 · Cited by 115 · see citing works
(2004) · Monographs of the Society for Research in Child Development · doi:10.1111/j.0037-976x.2004.00312.x · Cited by 112 · see citing works
Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior
Ferris, C. F., Lu, S., Messenger, T. L., Guillon, C. D., Heindel, N. D., Miller, M., KOPPEL, G. A., Bruns, F., & Simon, N. G. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.01.001 · Cited by 111 · see citing works
Predictors and sequelae of trajectories of physical aggression in school-age boys and girls
Campbell, S. B. G., Spieker, S. J., Vandergrift, N., Belsky, J., & Burchinal, M. A. (2010) · Development and Psychopathology · doi:10.1017/s0954579409990319 · Cited by 109 · see citing works
DNA methylation as a risk factor in the effects of early life stress
Kinnally, E. L., Feinberg, C., Kim, D. S., Ferguson, K., Leibel, R. L., Coplan, J. D., & Mann, J. J. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.05.001 · Cited by 99 · see citing works
Vaughn, M. G., DeLisi, M., Beaver, K. M., & WRIGHT, J. P. (2009) · Criminal Justice and Behavior · doi:10.1177/0093854809342839 · Cited by 90 · see citing works
DNA Methylome of Familial Breast Cancer Identifies Distinct Profiles Defined by Mutation Status
Flanagan, J. M., Cocciardi, S., Waddell, N., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.008 · Cited by 83 · see citing works
Brendgen, M., Boivin, M., Vitaro, F., Bukowski, W. M., Dionne, G., Tremblay, R., & Perusse, D. (2008) · Child Development · doi:10.1111/j.1467-8624.2007.01108.x · Cited by 82 · see citing works
Self-citationMurphy, D. M., Buckley, P. G., Bryan, K. R., Das, S., Alcock, L., Foley, N. H., Prenter, S., Bray, I. M., Watters, K. M., Higgins, D. G., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008154 · Cited by 82 · see citing works
Lempiäinen, H., Müller, A., Brasa, S., Teo, S.-S., Roloff, T. C., Morawiec, L., Zamurovic, N., Vicart, A., Funhoff, E. G., Couttet, P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018216 · Cited by 81 · see citing works
Falkenberg, V. R., Gurbaxani, B. M., Unger, E. R., & Rajeevan, M. S. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-010-8138-2 · Cited by 77 · see citing works
Vasopressin/oxytocin and aggression
Ferris, C. F. (2005) · Novartis Foundation symposium · doi:10.1002/0470010703.ch13 · Cited by 76 · see citing works
Provençal, N., Suderman, M. J., Caramaschi, D., Wang, D., Hallett, M. T., Vitaro, F., Tremblay, R. E., & Szyf, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071691 · Cited by 65 · see citing works
Self-citationAssociation of dopamine‐ and serotonin‐related genes with canine aggression
Våge, J., Wade, C., Biagi, T., Fatjó, J., Amat, M., Lindblad-Toh, K., & Lingaas, F. (2010) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2010.00568.x · Cited by 65 · see citing works
Kokko, K., Pulkkinen, L., Huesmann, L. R., Dubow, E. F., & Boxer, P. (2009) · Journal of Research on Adolescence · doi:10.1111/j.1532-7795.2009.00579.x · Cited by 64 · see citing works
Hassanain, M., Bhatt, S., Zalcman, S. S., & Siegel, A. (2005) · Brain Research · doi:10.1016/j.brainres.2005.04.086 · Cited by 63 · see citing works
Alleva, E., Cirulli, F., Bianchi, M., Bondiolotti, G., Chiarotti, F., Acetis, L. D., & Panerai, A. E. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00377.x · Cited by 59 · see citing works
Berlivet, S., Moussette, S., Ouimet, M., Verlaan, D. J., Koka, V., Tuwaijri, A. A., Kwan, T., Sinnett, D., Pastinen, T., & Naumova, A. K. (2012) · Human Genetics · doi:10.1007/s00439-012-1142-x · Cited by 57 · see citing works
Developmental Origins of Chronic Physical Aggression and Epigenetics
Tremblay, R. E., & Moshe Szyf, A. (2010) · Epigenomics · doi:10.2217/epi.10.40 · Cited by 54 · see citing works
Self-citationMonoamines, GABA, Glutamate, and Aggression
Miczek, K. A., & Fish, E. W. (2005) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195168761.003.0005 · Cited by 51 · see citing works
Hiura, H., Sugawara, A., Ogawa, H., John, R. M., Miyauchi, N., Miyanari, Y., Horiike, T., Li, Y., Yaegashi, N., Sasaki, H., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq200 · Cited by 51 · see citing works
Family Transmission and Heritability of Externalizing Disorders: A Twin-Family Study
Hicks, B. M., Krueger, R. F., Iacono, W. G., McGue, M., & Patrick, C. J. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.9.922 · Cited by 46 · see citing works
Hiura, H., Sugawara, A., Ogawa, H., John, R. M., Miyauchi, N., Miyanari, Y., Horiike, T., Li, Y., Yaegashi, N., Sasaki, H., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku624 · Cited by 44 · see citing works
Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma
Provençal, N., Suderman, M. J., Vitaro, F., Szyf, M., & Tremblay, R. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069481 · Cited by 40 · see citing works
Self-citationBiological role of interleukin-1beta in defensive-aggressive behaviour.
Pesce, M., Speranza, L., Franceschelli, S., Ialenti, V., Patruno, A., Febo, M., Lutiis, M. A. D., Felaco, M., & Grilli, A. (2011) · PubMed · Cited by 34 · see citing works
Navarro, J. F., Postigo, D., Martín‐López, M., & Burón, E. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.08.055 · Cited by 33 · see citing works
Tsui, D. W. Y., Lam, Y. M. D., Lee, W. S., Leung, T. Y., Lau, T. K., Lau, E. T., Tang, M. H. Y., Akolekar, R., Nicolaides, K. H., Chiu, R. W. K., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015069 · Cited by 31 · see citing works
Stomach – Genetic and epigenetic alterations of preneoplastic and neoplastic lesions
David, S., & Meltzer, S. J. (2011) · Cancer Biomarkers · doi:10.3233/cbm-2011-0169 · Cited by 27 · see citing works
Tomazou, E. M., Rakyan, V. K., Lefebvre, G. C., Andrews, R., Ellis, P., Jackson, D. K., Langford, C., Francis, M. D., Bäckdahl, L., Miretti, M. M., et al. (2008) · BMC Medical Genomics · doi:10.1186/1755-8794-1-19 · Cited by 27 · see citing works
Jinsong, J., Pękowska, A., Jaeger, S., Benoukraf, T., Ferrier, P., & Spicuglia, S. (2010) · BMC Research Notes · doi:10.1186/1756-0500-3-240 · Cited by 24 · see citing works
Rajendram, R., Ferreira, J. C., Grafodatskaya, D., Choufani, S., Chiang, T., Pu, S., Butcher, D. T., Wodak, S. J., & Weksberg, R. (2011) · Epigenetics · doi:10.4161/epi.6.4.14763 · Cited by 22 · see citing works
Pathway analysis following association study
Ngwa, J. S., Manning, A. K., Grimsby, J., Lu, C., Zhuang, W. V., & DeStefano, A. L. (2011) · BMC Proceedings · doi:10.1186/1753-6561-5-s9-s18 · Cited by 22 · see citing works
Zhang, S. (2007) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1246 · Cited by 20 · see citing works
Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array
Yang, L., Zhang, K., Dai, W., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-10 · Cited by 17 · see citing works
Generalization of DNA microarray dispersion properties: microarray equivalent of t-distribution.
Novak, J. P., Kim, S., Xu, J., Modlich, O., Volsky, D. J., Honys, D., Slonczewski, J. L., Bell, D. A., Blattner, F. R., Blumwald, E., et al. (2006) · Biology Direct · doi:10.1186/1745-6150-1-27 · Cited by 16 · see citing works
Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice
Yukawa, K., Iso, H., Tanaka, T., et al. (2005) · International Journal of Molecular Medicine · doi:10.3892/ijmm.15.5.819 · Cited by 14 · see citing works
Mack, A. H. (2012) · Yearbook of Psychiatry and Applied Mental Health · doi:10.1016/j.ypsy.2012.07.061 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms
Waltes, R., Chiocchetti, A. G., & Freitag, C. M. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32388 · Cited by 182 · see citing works
Barker, E. D., Walton, E., & Cecil, C. A. M. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12782 · Cited by 134 · see citing works
Vaiserman, A. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0130-0 · Cited by 91 · see citing works
Epigenetic programming by early-life stress
Alyamani, R. A. S., & Murgatroyd, C. (2018) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2018.01.004 · Cited by 76 · see citing works
Zhou, A., & Ryan, J. (2023) · Genes · doi:10.3390/genes14081639 · Cited by 57 · see citing works
“A genome-wide study of men found that parental physical aggression in childhood and adolescence was associated with differential methylation in genes previously implicated in aggressive behavior [50].”
BackgroundEpigenetics and gene expression profile in first-episode psychosis: the role of childhood trauma
Tomassi, S., & Tosato, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.10.018 · Cited by 51 · see citing works
Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study
Cecil, C. A. M., Walton, E., Jaffee, S. R., O'Connor, T., Maughan, B., Relton, C. L., Smith, R. G., McArdle, W., Gaunt, T. R., Ouellet-Morin, I., et al. (2018) · Development and Psychopathology · doi:10.1017/s095457941700092x · Cited by 46 · see citing works
Genetics of child aggression, a systematic review
Koyama, E., Kant, T., Takata, A., Kennedy, J. L., & Zai, C. C. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02870-7 · Cited by 33 · see citing works
Epigenetics, early adversity and child and adolescent mental health
Barker, E. D. (2018) · Psychopathology · doi:10.1159/000486683 · Cited by 21 · see citing works
Vollebregt, O., Koyama, E., Zai, C. C., Shaikh, S. A., Lisoway, A. J., Kennedy, J. L., & Beitchman, J. H. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.05.062 · Cited by 13 · see citing works
Cao-Lei, L., Elgbeili, G., Massart, R., Laplante, D. P., Szyf, M., & King, S. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.13 · Cited by 98 · see citing works
Self-citation
- Authors
- Provençal, N., Suderman, M. J., Guillemin, C., Vitaro, F., Côté, S. M., Hallett, M., Tremblay, R. E., & Szyf, M.
- Affiliations
- Research Unit on Children's Psychosocial Maladjustment (CA)
- McGill University (CA)
- University College Dublin (IE)
- Corresponding author
- Tremblay, Richard E.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-04-01
- Volume
- 9
- Issue
- 4
- Pages
- e89839
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3972178
- OpenAlex
- W2080011484
- Cited by
- 85
- References
- 114
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 13 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 2
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Canadian Institute for Advanced Research
- McGill University
- Canadian Institutes of Health Research (42411, MOP42411)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- child aggression, DNA methylation, promoter methylation, T cells, epigenetics, early childhood adversity, microRNA, adult male
- MeSH terms
- Adult, Aggression, Child, Chromosomes, Human, Female, Humans, Male, Promoter Regions, Genetic, T-Lymphocytes, Genome, Human, Cluster Analysis, Case-Control Studies, CpG Islands, DNA Methylation
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
