DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament

BACKGROUND DNA methylation of the differentially methylated regions (DMRs) of imprinted genes is relevant to neurodevelopment. METHODS DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158). RESULTS MEG3 DMR levels were positively associated with internalizing (β = 0.15, P = 0.044) and surgency (β = 0.19, P = 0.018) behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the intergenic MEG3-IG methylation regions were associated with surgency (β = 0.28, P = 0.0003) and PEG3 was positively related to externalizing (β = 0.20, P = 0.01) and negative affectivity (β = 0.18, P = 0.02). CONCLUSION While the small sample size limits inference, these pilot data support gene-specific associations between epigenetic differences in regulatory regions of imprinted domains at birth and later infant temperament.

[1]  M. Gorbatyuk,et al.  Neuronatin Protein in Health and Disease , 2017, Journal of cellular physiology.

[2]  Tom R. Gaunt,et al.  Prenatal unhealthy diet, insulin‐like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early‐onset conduct problems , 2016, Journal of child psychology and psychiatry, and allied disciplines.

[3]  L. Provenzi,et al.  SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature , 2016, Neuroscience & Biobehavioral Reviews.

[4]  Charles Auffray,et al.  DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. , 2016, American journal of human genetics.

[5]  M. Owen,et al.  Psychiatric disorders, myoclonus dystonia and SGCE: an international study , 2015, Annals of clinical and translational neurology.

[6]  R. Dixit,et al.  Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1 , 2015, The Journal of Neuroscience.

[7]  R. T. Lie,et al.  Identification of DNA Methylation Changes in Newborns Related to Maternal Smoking during Pregnancy , 2014, Environmental health perspectives.

[8]  E. Iversen,et al.  Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort , 2014, Epigenetics.

[9]  R. Joseph.  Neuronatin gene: Imprinted and misfolded: Studies in Lafora disease, diabetes and cancer may implicate NNAT-aggregates as a common downstream participant in neuronal loss. , 2014, Genomics.

[10]  A. Hofman,et al.  DNA methylation profiles at birth and child ADHD symptoms. , 2014, Journal of psychiatric research.

[11]  E. Iversen,et al.  Maternal Stress, Preterm Birth, and DNA Methylation at Imprint Regulatory Sequences in Humans , 2014, Genetics & epigenetics.

[12]  A. Ronald,et al.  “He who sees things grow from the beginning will have the finest view of them” A systematic review of genetic studies on psychological traits in infancy , 2013, Neuroscience & Biobehavioral Reviews.

[13]  L. Wilkinson,et al.  Placental programming of anxiety in adulthood revealed by Igf2-null models , 2013, Nature Communications.

[14]  B. Lester,et al.  Placental HTR2A methylation is associated with infant neurobehavioral outcomes , 2013, Epigenetics.

[15]  V. Vaccarino,et al.  Association Between Promoter Methylation of Serotonin Transporter Gene and Depressive Symptoms: A Monozygotic Twin Study , 2013, Psychosomatic medicine.

[16]  S. Murphy,et al.  DNA methylation at imprint regulatory regions in preterm birth and infection. , 2013, American journal of obstetrics and gynecology.

[17]  B. Bradley,et al.  Differential Genetic and Epigenetic Regulation of catechol-O-methyltransferase is Associated with Impaired Fear Inhibition in Posttraumatic Stress Disorder , 2013, Frontiers in Behavioral Neuroscience.

[18]  D. Klein,et al.  Gender differences in young children's temperament traits: comparisons across observational and parent-report methods. , 2013, Journal of personality.

[19]  S. Murphy,et al.  Associations between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer , 2013, PloS one.

[20]  S. Murphy,et al.  Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues , 2012, PloS one.

[21]  E. Iversen,et al.  Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements , 2012, Epigenetics.

[22]  Sabine J. Roza,et al.  Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study. , 2012, The American journal of clinical nutrition.

[23]  B. Lester,et al.  Placenta-imprinted gene expression association of infant neurobehavior. , 2012, The Journal of pediatrics.

[24]  E. Iversen,et al.  Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke. , 2012, Gene.

[25]  M. Cairns,et al.  Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells , 2011, Molecular Psychiatry.

[26]  L. DiLalla,et al.  Social-emotional development through a behavior genetics lens: infancy through preschool. , 2012, Advances in child development and behavior.

[27]  Kirsten R. McEwen,et al.  Postnatal loss of Dlk1 imprinting in stem cells and niche-astrocytes regulates neurogenesis , 2011, Nature.

[28]  M. Ungless,et al.  DLK1 Promotes Neurogenesis of Human and Mouse Pluripotent Stem Cell-Derived Neural Progenitors Via Modulating Notch and BMP Signalling , 2011, Stem Cell Reviews and Reports.

[29]  E. Kopsida,et al.  The role of imprinted genes in mediating susceptibility to neuropsychiatric disorders , 2011, Hormones and Behavior.

[30]  S. Murphy,et al.  Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST) , 2011, BMC public health.

[31]  K. Kernohan,et al.  Genetic and epigenetic dysregulation of imprinted genes in the brain. , 2010, Epigenomics.

[32]  A. Prentice,et al.  Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles , 2010, PLoS genetics.

[33]  J. Ormel,et al.  Evidence for plasticity genotypes in a gene–gene–environment interaction: the TRAILS study , 2010, Genes, brain, and behavior.

[34]  S. Bilbo,et al.  Enduring consequences of maternal obesity for brain inflammation and behavior of offspring , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  A. Green,et al.  The IG-DMR and the MEG3-DMR at Human Chromosome 14q32.2: Hierarchical Interaction and Distinct Functional Properties as Imprinting Control Centers , 2010, PLoS genetics.

[36]  D. Sassoon,et al.  Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development , 2010, Nature Cell Biology.

[37]  Margaret J. Briggs-Gowan,et al.  Internalizing Trajectories in Young Boys and Girls: The Whole is Not a Simple Sum of its Parts , 2010, Journal of abnormal child psychology.

[38]  S. Murphy,et al.  Imprint regulatory elements as epigenetic biosensors of exposure in epidemiological studies , 2009, Journal of Epidemiology & Community Health.

[39]  Tracy L. Spinrad,et al.  Longitudinal relations of children's effortful control, impulsivity, and negative emotionality to their externalizing, internalizing, and co-occurring behavior problems. , 2009, Developmental psychology.

[40]  E. Keverne,et al.  Paternal influence on female behavior: the role of Peg3 in exploration, olfaction, and neuroendocrine regulation of maternal behavior of female mice. , 2009, Behavioral neuroscience.

[41]  E. Keverne,et al.  Increased apoptosis during neonatal brain development underlies the adult behavioral deficits seen in mice lacking a functional paternally expressed gene 3 (Peg3) , 2009, Developmental neurobiology.

[42]  Gustavo Turecki,et al.  Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse , 2009, Nature Neuroscience.

[43]  S. Wiebe,et al.  Gene-environment interactions across development: Exploring DRD2 genotype and prenatal smoking effects on self-regulation. , 2009, Developmental psychology.

[44]  Hein Putter,et al.  Persistent epigenetic differences associated with prenatal exposure to famine in humans , 2008, Proceedings of the National Academy of Sciences.

[45]  E. Keverne,et al.  The paternally expressed gene Peg3 regulates sexual experience-dependent preferences for estrous odors. , 2008, Behavioral neuroscience.

[46]  V. Perry,et al.  Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring , 2008, The Journal of physiology.

[47]  L. Wilkinson,et al.  What Are Imprinted Genes Doing in the Brain? , 2007, Advances in experimental medicine and biology.

[48]  P. Sullivan,et al.  Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype , 2008, Molecular Psychiatry.

[49]  R. Jirtle,et al.  Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases , 2007, Pediatric Research.

[50]  N. Blom,et al.  Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation , 2007, Experimental Neurology.

[51]  M. Rothbart,et al.  Measurement of fine-grained aspects of toddler temperament: the early childhood behavior questionnaire. , 2006, Infant behavior & development.

[52]  B. Tycko,et al.  Regulation of placental efficiency for nutrient transport by imprinted genes. , 2006, Placenta.

[53]  K. Saudino.  Behavioral Genetics and Child Temperament , 2005, Journal of developmental and behavioral pediatrics : JDBP.

[54]  L. Harper,et al.  Epigenetic inheritance and the intergenerational transfer of experience. , 2005, Psychological bulletin.

[55]  L. Wilkinson,et al.  Imprinted Nesp55 Influences Behavioral Reactivity to Novel Environments , 2005, Molecular and Cellular Biology.

[56]  Todd D. Little,et al.  The Infant–Toddler Social and Emotional Assessment (ITSEA): Factor Structure, Reliability, and Validity , 2003, Journal of abnormal child psychology.

[57]  J. Buitelaar,et al.  Psychological measures of prenatal stress as predictors of infant temperament. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[58]  J. Kagan,et al.  Further evidence of association between behavioral inhibition and social anxiety in children. , 2001, The American journal of psychiatry.

[59]  S. Murphy,et al.  Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. , 2000, Genome research.

[60]  M. Azim Surani,et al.  Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest , 1998, Nature Genetics.

[61]  S. Cichon,et al.  Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain. , 1998, Brain research. Molecular brain research.

[62]  J. Paszkowski,et al.  The genetics of epigenetics. , 1998, Current biology : CB.

[63]  N. Jenkins,et al.  Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages. , 1996, Developmental biology.