Ancestral experience as a game changer in stress vulnerability and disease outcomes

BioEssays

Volumn 37, Issue 6, 2015, Pages 602-611

  Metz, Gerlinde A S ^a   Ng, Jane W Y ^b   Kovalchuk, Igor ^c   Olson, David M ^d  

^a UNIVERSITY OF LETHBRIDGE   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c UNIVERSITY OF LETHBRIDGE   (Canada)

^d UNIVERSITY OF ALBERTA   (Canada)

Author keywords

DNA methylation; Epigenetics; Mental health; MicroRNA; Neurological disease; Prenatal stress programming; Transgenerational epigenetic inheritance

Indexed keywords

BIOLOGICAL MARKER; MICRORNA;

ANCESTRAL EXPERIENCE; ANCESTRY GROUP; DATA MINING; EPIGENETICS; EXPERIENCE; GRANDPARENT; HEALTH; HUMAN; HYPOTHESIS; INFORMATION; INFORMATION PROCESSING; LIFESPAN; NONHUMAN; OUTCOME ASSESSMENT; PARENT; PERSONALIZED MEDICINE; PREDICTION; PRENATAL STRESS; PROPHYLAXIS; REVIEW; RISK; STRESS; ANIMAL; COMPLICATION; FEMALE; GENETIC EPIGENESIS; GENOME IMPRINTING; MENTAL STRESS; METABOLISM; PHYSIOLOGY; PREGNANCY; PRENATAL EXPOSURE; RNA INTERFERENCE;

ANIMALS; EPIGENESIS, GENETIC; FEMALE; GENOMIC IMPRINTING; HUMANS; MICRORNAS; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RNA INTERFERENCE; STRESS, PSYCHOLOGICAL;

EID: 84929504855     PISSN: 02659247     EISSN: 15211878     Source Type: Journal    
DOI: 10.1002/bies.201400217     Document Type: Review

References (118)

1. Franklin TB, Saab BJ, Mansuy IM. 2012. Neural mechanisms of stress resilience and vulnerability. Neuron 75: 747-61.
2. Migicovsky Z, Kovalchuk I. 2011. Epigenetic memory in mammals. Front Genet 2: 28.
3. Cottrell EC, Seckl JR. 2009. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 3: 1-9.
4. Sun K, Yang K, Challis JR. 1997. Differential expression of 11 beta-hydroxysteroid dehydrogenase types 1 and 2 in human placenta and fetal membranes. J Clin Endocrinol Metab 82: 300-5.
5. Welberg LA, Thrivikraman KV, Plotsky PM. 2005. Chronic maternal stress inhibits the capacity to up-regulate placental 11beta-hydroxysteroid dehydrogenase type 2 activity. J Endocrinol 186: R7-12.
6. Hompes T, Izzi B, Gellens E, Morreels M, et al. 2013. Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. J Psychiatr Res 47: 880-91.
7. Szyf M, Weaver IC, Champagne FA, Diorio J, et al. 2005. Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat. Front Neuroendocrinol 26: 139-62.
8. Rakers F, Frauendorf V, Rupprecht S, Schiffner R, et al. 2013. Effects of early- and late-gestational maternal stress and synthetic glucocorticoid on development of the fetal hypothalamus-pituitary-adrenal axis in sheep. Stress 16: 122-9.
9. Schwab M. 2009. Intrauterine programming of disorders of brain function in later life. Gynakol Geburtshilfliche Rundsch 49: 13-28.
10. Christiaens I, Olson DM, Metz GA. 2014. Stress and preterm birth. In Zhang L, Longo LD, ed; Stress and developmental programming of health and disease: beyond phenomenology. New York: Nova Science Publishers. p. 509-40.
11. Betts KS, Williams GM, Najman JM, Scott J, et al. 2014. Exposure to stressful life events during pregnancy predicts psychotic experiences via behaviour problems in childhood. J Psychiatr Res S0022-3956: 00237-4.
12. Walder DJ, Laplante DP, Sousa-Pires A, Veru F, et al. 2014. Prenatal maternal stress predicts autism traits in 61/2 year-old children: Project Ice Storm. Psychiatry Res 219: 353-60.
13. Pallarés ME, Antonelli MC. 2015. Hormonal modulation of catecholaminergic neurotransmission in a prenatal stress model. Adv Neurobiol 10: 45-9.
14. Uban KA, Comeau WL, Ellis LA, Galea LA, et al. 2013. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress. Psychoneuroendocrinology 38: 1953-66.
15. Mueller BR, Bale TL. 2008. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 28: 9055-65.
16. Rodgers AB, Morgan CP, Bronson SL, Revello S, et al. 2013. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 33: 9003-12.
17. Muhammad A, Carroll C, Kolb B. 2012. Stress during development alters dendritic morphology in the nucleus accumbens and prefrontal cortex. Neuroscience 216: 103-9.
18. Pawluski JL, Valença A, Santos AI, Costa-Nunes JP, et al. 2012. Pregnancy or stress decrease complexity of CA3 pyramidal neurons in the hippocampus of adult female rats. Neuroscience 227: 201-10.
19. Coe CL, Kramer M, Czéh B, Gould E, et al. 2003. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol Psychiatry 54: 1025-34.
20. Antonow-Schlorke I, Helgert A, Gey C, Coksaygan T, et al. 2009. Adverse effects of antenatal glucocorticoids on cerebral myelination in sheep. Obstet Gynecol 113: 142-51.
21. Raschke C, Schmidt S, Schwab M, Jirikowski G. 2008. Effects of betamethasone treatment on central myelination in fetal sheep: an electron microscopical study. Anat Histol Embryol 37: 95-100.
22. Cullen AE, Zunszain PA, Dickson H, Roberts RE, et al. 2014. Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: relationship to psychosocial stress and cognition. Psychoneuroendocrinology 46: 1-13.
23. Raison CL, Miller AH. 2011. Is depression an inflammatory disorder? Curr Psychiatry Rep 13: 467-75.
24. Grippo AJ, Johnson AK. 2009. Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models. Stress 12: 1-21.
25. Tyrka AR, Walters OC, Price LH, Anderson GM, et al. 2012. Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults. Horm Metab Res 44: 543-9.
26. Gragnoli C. 2014. Hypothesis of the neuroendocrine cortisol pathway gene role in the comorbidity of depression, type 2 diabetes, and metabolic syndrome. Appl Clin Genet 7: 43-53.
27. Smith LK, Jadavji NM, Colwell KL, Katrina Perehudoff S, et al. 2008. Stress accelerates neural degeneration and exaggerates motor symptoms in a rat model of Parkinson's disease. Eur J Neurosci 27: 2133-46.
28. Gadek-Michalska A1, Tadeusz J, Rachwalska P, Bugajski J. 2013. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep 65: 1655-62.
29. Grinevich V, Ma XM, Herman JP, Jezova D, et al. 2001. Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. J Neuroendocrinol 13: 711-23.
30. Pinnock SB, Herbert J. 2001. Corticosterone differentially modulates expression of corticotropin releasing factor and arginine vasopressin mRNA in the hypothalamic paraventricular nucleus following either acute or repeated restraint stress. Eur J Neurosci 13: 576-84.
31. Braconi C, Huang N, Patel T. 2010. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology 51: 881-90.
32. Boyko A, Blevins T, Yao Y, Golubov A, et al. 2010. Transgenerational adaptation of Arabidopsis to stress requires DNA methylation and the function of Dicer-like proteins. PloS ONE 5: e9514.
33. Relton CL, Davey Smith G. 2010. Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. PLoS Med 7: e1000356.
34. Babenko O, Golubov A, Ilnytskyy Y, Kovalchuk I, et al. 2012. Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming. PLoS ONE 7: e29441.
35. Bale TL. 2014. Lifetime stress experience: transgenerational epigenetics and germ cell programming. Dialogues Clin Neurosci 16: 297-305.
36. Franklin TB, Russig H, Weiss IC, Gräff J, et al. 2010. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 68: 408-15.
37. Babenko O, Kovalchuk I, Metz GA. 2012. Epigenetic programming of neurodegenerative diseases by an adverse environment. Brain Res 1444: 96-111.
38. Heller EA, Cates HM, Peña CJ, Sun H, et al. 2014. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci 17: 1720-7.
39. Pausova Z, Tremblay J, Hamet P. 1999. Gene-environment interactions in hypertension. Curr Hypertens Rep 1: 42-50.
40. Waterland RA, Jirtle RL. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23: 5293-300.
41. Dolinoy DC, Huang D, Jirtle RL. 2007. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA 104: 13056-61.
42. Drake A, Walker B. 2004. The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol 180: 1-16.
43. Lopez-Jaramillo P. 2009. Cardiometabolic disease in Latin America: the role of fetal programming in response to maternal malnutrition. Rev Esp Cardiol 62: 670-6.
44. Van den Bergh BR, Loomans EM, Mennes M. 2015. Early life influences on cognition, behavior, and emotion in humans: from birth to age 20. Adv Neurobiol 10: 315-31.
45. Van den Bergh BR, Mennes M, Oosterlaan J, Stevens V, et al. 2005. High antenatal maternal anxiety is related to impulsivity during performance on cognitive tasks in 14- and 15-year-olds. Neurosci Biobehav Rev 29: 259-69.
46. Van den Bergh BR, Van Calster B, Smits T, Van Huffel S, et al. 2008. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: a prospective study on the fetal origins of depressed mood. Neuropsychopharmacology 33: 536-45.
47. Brand SR, Engel SM, Canfield RL, Yehuda R. 2006. The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant. Ann N Y Acad Sci 1071: 454-8.
48. Sarapas C, Cai G, Bierer LM, Golier JA, et al. 2011. Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers 30: 101-10.
49. Binder EB. 2009. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34: S186-95.
50. King S, Dancause K, Turcotte-Tremblay AM, Veru F, et al. 2012. Using natural disasters to study the effects of prenatal maternal stress on child health and development. Birth Defects Res C Embryo Today 96: 273-88.
51. Laplante DP, Brunet A, Schmitz N, Ciampi A, et al. 2008. Project Ice Storm: prenatal maternal stress affects cognitive and linguistic functioning in 5 1/2-year-old children. J Am Acad Child Adolesc Psychiatry 47: 1063-72.
52. Cao-Lei L, Massart R, Suderman MJ, Machnes Z, et al. 2014. DNA methylation signatures triggered by prenatal maternal stress exposure to a natural disaster: project ice storm. PLoS ONE 9: e107653.
53. Boyd A, Golding J, Macleod J, Lawlor DA, et al. 2013. Cohort Profile: the 'children of the 90s'-the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 42: 111-27.
54. O'Donnell KJ, Glover V, Jenkins J, Browne D, et al. 2013. Prenatal maternal mood is associated with altered diurnal cortisol in adolescence. Psychoneuroendocrinology 38: 1630-8.
55. Vedhara K, Metcalfe C, Brant H, Crown A, et al. 2012. Maternal mood and neuroendocrine programming: effects of time of exposure and sex. J Neuroendocrinol 24: 999-1011.
56. Morales E, Groom A, Lawlor DA, Relton CL. 2014. DNA methylation signatures in cord blood associated with maternal gestational weight gain: results from the ALSPAC cohort. BMC Res Notes 7: 278.
57. Richmond RC, Al-Amin A, Davey Smith G, Relton CL, 2014. Approaches for drawing causal inferences from epidemiological birth cohorts: a review. Early Hum Dev 90: 769-80.
58. Painter RC, Osmond C, Gluckman P, Hanson M, et al. 2008. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG 115: 1243-9.
59. de Rooij SR, Wouters H, Yonker JE, Painter RC, et al. 2010. Prenatal undernutrition and cognitive function in late adulthood. Proc Natl Acad Sci USA 107: 16881-6.
60. Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, et al. 2000. Coronary heart disease after prenatal exposure to the Dutch famine, 1944-45. Heart 84: 595-8.
61. Heijmans BT, Tobi EW, Stein AD, Putter H, et al. 2008. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 105: 17046-9.
62. Tobi EW, Goeman JJ, Monajemi R, Gu H, et al. 2014. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 5: 5592.
63. Bygren LO, Tinghög P, Carstensen J, Edvinsson S, et al. 2014. Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet 15: 12.
64. Bygren LO, Kaati G, Edvinsson S. 2001. Longevity determined by paternal ancestors' nutrition during their slow growth period. Acta Biotheor 49: 53-9.
65. Kaati G, Bygren LO, Edvinsson S. 2002. Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur J Hum Genet 10: 682-8.
66. Stern S, Fridmann-Sirkis Y, Braun E, Soen Y. 2012. Epigenetically heritable alteration of fly development in response to toxic challenge. Cell Rep 1: 528-42.
67. Morgan DK, Whitelaw E. 2008. The case for transgenerational epigenetic inheritance in humans. Mamm Genome 19: 394-7.
68. Pembrey M, Saffery R, Bygren LO, Network in Epigenetic Epidemiology. 2014. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet. 51: 563-72.
69. Cheng L, Doecke JD, Sharples RA, Villemagne VL, et al. 2014. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment. Mol Psychiatry, in press, doi: 10.1038/mp.2014.127
70. Koch MW, Metz LM, Kovalchuk O. 2013. Epigenetics and miRNAs in the diagnosis and treatment of multiple sclerosis. Trends Mol Med 19: 23-30.
71. Koturbash I, Zemp FJ, Pogribny I, Kovalchuk O. 2011. Small molecules with big effects: the role of the microRNAome in cancer and carcinogenesis. Mutat Res 722: 94-105.
72. Krichevsky AM, King KS, Donahue CP, Khrapko K, et al. 2003. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9: 1274-81.
73. Schratt GM, Tuebing F, Nigh EA, Kane CG, et al. 2006. A brain-specific microRNA regulates dendritic spine development. Nature 439: 283-9.
74. Nesler KR, Sand RI, Symmes BA, Pradhan SJ, et al. 2013. The miRNA pathway controls rapid changes in activity-dependent synaptic structure at the Drosophila melanogaster neuromuscular junction. PLoS ONE 8: e68385.
75. Tsang J, Zhu J, van Oudenaarden A. 2007. MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell 26: 753-67.
76. Chavali V, Tyagi SC, Mishra PK. 2012. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun 425: 668-72.
77. Sinkkonen L, Hugenschmidt T, Berninger P, Gaidatzis D, et al. 2008. MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells. Nat Struct Mol Biol 15: 259-67.
78. Yoo AS, Staahl BT, Chen L, Crabtree GR. 2009. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460: 642-6.
79. Haapa-Paananen S, Chen P, Hellström K, Kohonen P, et al. 2013. Functional profiling of precursor microRNAs identifies microRNAs essential for glioma proliferation. PLoS ONE 8: e60930.
80. Noorbakhsh F, Ellestad KK, Maingat F, Warren KG, et al. 2011. Impaired neurosteroid synthesis in multiple sclerosis. Brain 134: 2703-21.
81. Ikeda S, Kong SW, Lu J, Bisping E, et al. 2007. Altered microRNA expression in human heart disease. Physiol Genomics 31: 367-73.
82. Jansen F, Yang X, Proebsting S, Hoelscher M, et al. 2014. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc 3: e001249.
83. Doridot L, Houry D, Gaillard H, Chelbi ST, et al. 2014. MiR-34a expression, epigenetic regulation, and function in human placental diseases. Epigenetics 9: 142-51.
84. Renthal NE, Chen CC, Williams KC, Gerard RD, et al. 2010. MiR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci USA 107: 20828-33.
85. Koshiol J, Wang E, Zhao Y, Marincola F, et al. 2010. Strengths and limitations of laboratory procedures for microRNA detection. Cancer Epidemiol Biomarkers Prev 19: 907-11.
86. Drake AJ, Seckl JR. 2011. Transmission of programming effects across generations. Pediatr Endocrinol Rev 9: 566-78.
87. Skinner MK. 2014. Environmental stress and epigenetic transgenerational inheritance. BMC Med 12: 153.
88. Zucchi FC, Yao Y, Ward ID, Ilnytskyy Y, et al. 2013. Maternal stress induces epigenetic signatures of psychiatric and neurological diseases in the offspring. PLoS ONE 8: e56967.
89. Yao Y, Robinson AM, Zucchi FC, Robbins JC, et al. 2014. Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC Med 12: 121.
90. Skinner MK. 2008. What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol 25: 2-6.
91. Gapp K, Jawaid A, Sarkies P, Bohacek J, et al. 2014. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature Neurosci 17: 667-9.
92. Rechavi O, Houri-Ze'evi L, Anava S, Goh WS, et al. 2014. Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell 158: 277-87.
93. Barker DJ. 2007. The origins of the developmental origins theory. J Intern Med 261: 412-27.
94. Ng JWY, Relton CL, Olson DM. 2014. DNA methylation evidence links maternal smoking with pre- and post-natal growth. Abstract at the Canadian National Perinatal Research Meeting, Banff, Canada.
95. Suter M, Ma J, Harris A, Patterson L, et al. 2011. Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression. Epigenetics 6: 1284-94.
96. Rodríguez-Antona C, Taron M. 2015. Pharmacogenomic biomarkers for personalized cancer treatment. J Intern Med 277: 201-17.
97. Smith N, Nucera C. 2015. Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations. J Clin Endocrinol Metab 100: 35-42.
98. Keller A, Leidinger P, Lange J, Borries A, et al. 2009. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS ONE 4: e7440.
99. Weber M, Baker MB, Patel RS, Quyyumi AA, et al. 2011. MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB. Cardiol Res Pract 2011: 532915.
100. Wolfe B, Haveman R, Ginther D, An CB. 1996. The "window problem" in studies of children's attainments: A Methodological Exploration. J Am Statistical Assoc 91: 970-82.
101. Golding J. 1990. Children of the nineties. A longitudinal study of pregnancy and childhood based on the population of Avon (ALSPAC). West Engl Med J 105: 80-2.
102. Gottesman II, Gould TD. 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160: 636-45.
103. Boyles AL, DeRoo LA, Lie RT, Taylor JA, et al. 2010. Maternal alcohol consumption, alcohol metabolism genes, and the risk of oral clefts: a population-based case-control study in Norway, 1996-2001. Am J Epidemiol 172: 924-31.
104. Herman AI, Sofuoglu M. 2010. Cognitive effects of nicotine: genetic moderators. Addict Biol 15: 250-65.
105. Relton CL, Davey Smith G. 2012. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol 41: 161-76.
106. Liu JZ, Tozzi F, Waterworth DM, Pillai SG, et al. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 42: 436-40.
107. Freathy RM, Ring SM, Shields B, Galobardes B, et al. 2009. A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy. Hum Mol Genet 18: 2922-7.
108. Smith GD, Lawlor DA, Harbord R, Timpson N, et al. 2007. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med 4: e552.
109. Clayton D, McKeigue PM. 2001. Epidemiological methods for studying genes and environmental factors in complex diseases. Lancet 58: 1356-60.
110. Rubin TG, Gray JD, McEwen BS. 2014. Experience and the ever-changing brain: what the transcriptome can reveal. BioEssays 36: 1072-81.
111. Linsel-Nitschke P, Götz A, Erdmann J, Braenne I, et al. 2008. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease-a Mendelian Randomisation study. PLoS ONE 3: e2986.
112. Marcia M, Humphris-Narayanan E, Keating KS, Somarowthu S, et al. 2013. Solving nucleic acid structures by molecular replacement: examples from group II intron studies. Acta Crystallogr D Biol Crystallogr 69: 2174-85.
113. Merk A, Subramaniam S. 2013. HIV-1 envelope glycoprotein structure. Curr Opin Struct Biol 23: 268-76.
114. Kinnally EL, Feinberg C, Kim D, Ferguson K, et al. 2011. DNA methylation as a risk factor in the effects of early life stress. Brain Behav Immun 25: 1548-53.
115. Michels KB, Harris HR, Barault L. 2011. Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. PLoS ONE 6: e25254.
116. Zhou X, Maricque B, Xie M, Li D, et al. 2011. The Human Epigenome Browser at Washington University. Nat Methods 8: 989-90.
117. Babenko O, Kovalchuk I, Metz GA. 2015. Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neurosci Biobehav Rev 48C: 70-91.
118. Geneletti SG, Gallo V, Porta M, Khoury MJ, et al. 2011. Assessing causal relationships in genomics: from Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs. Emerg Themes Epidemiol 8: 5.