title: DNA methylation profiles at birth and child ADHD symptoms.
abstract: Attention deficit/hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder. In addition, early life environmental factors contribute to the occurrence of ADHD. Recently, DNA methylation has emerged as a mechanism potentially mediating genetic and environmental effects. Here, we investigated whether newborn DNA methylation patterns of selected candidate genes involved in psychiatric disorders or fetal growth are associated with ADHD symptoms in childhood. Participants were 426 children from a large population based cohort of Dutch national origin. Behavioral data were obtained at age 6 years with the Child Behavior Checklist. For the current study, 11 regions at 7 different genes were selected. DNA methylation levels of cord blood DNA were measured for the 11 regions combined and for each region separately. We examined the association between DNA methylation levels at different regions and ADHD symptoms with linear mixed models. DNA methylation levels were negatively associated with ADHD symptom score in the overall analysis of all 11 regions. This association was largely explained by associations of DRD4 and 5-HTT regions. Other candidate genes showed no association between DNA methylation levels and ADHD symptom score. Associations between DNA methylation levels and ADHD symptom score were attenuated by co-occurring Oppositional defiant disorder and total symptoms. Lower DNA methylation levels of the 7 genes assessed at birth, were associated with more ADHD symptoms of the child at 6 years of age. Further studies are needed to confirm our results and to investigate the possible underlying mechanism.
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Obstetrics & Gynecology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Nina H
authors.initials: NH
authors.lastname: van Mil
authors.affiliation: Department of Obstetrics & Gynecology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Obstetrics & Gynecology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Marieke I
authors.initials: MI
authors.lastname: Bouwland-Both
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Michael M P J
authors.initials: MM
authors.lastname: Verbiest
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: Rijlaarsdam
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Obstetrics & Gynecology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.affiliation: Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Paul H C
authors.initials: PH
authors.lastname: Eilers
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Department of Psychiatry, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000503:physiopathology*; D001526:Behavioral Symptoms / Q000209:etiology; D001722:Birth Order; D001724:Birth Weight; D002648:Child; D015331:Cohort Studies; D018672:Community Health Planning; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D060005:Genotyping Techniques; D005865:Gestational Age; D006801:Humans; D016014:Linear Models; D008297:Male; D036801:Parturition; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C493599:DRD4 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4
keywords: Attention deficit/hyperactivity disorder; DNA methylation