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 eff...
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| Veröffentlicht in: | Journal of psychiatric research 2014-02, Vol.49, p.51-59 |
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| creator | van Mil, Nina H Steegers-Theunissen, Régine P.M Bouwland-Both, Marieke I Verbiest, Michael M.P.J Rijlaarsdam, Jolien Hofman, Albert Steegers, Eric A.P Heijmans, Bastiaan T Jaddoe, Vincent W.V Verhulst, Frank C Stolk, Lisette Eilers, Paul H.C Uitterlinden, André G Tiemeier, Henning |
| description | 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. |
| doi_str_mv | 10.1016/j.jpsychires.2013.10.017 |
| format | Article |
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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.</description><identifier>ISSN: 0022-3956</identifier><identifier>EISSN: 1879-1379</identifier><identifier>DOI: 10.1016/j.jpsychires.2013.10.017</identifier><identifier>PMID: 24290898</identifier><identifier>CODEN: JPYRA3</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Attention Deficit Disorder with Hyperactivity - epidemiology ; Attention Deficit Disorder with Hyperactivity - physiopathology ; Attention deficit disorders. Hyperactivity ; Attention deficit hyperactivity disorder ; Behavioral Symptoms - etiology ; Biological and medical sciences ; Birth Order ; Birth Weight ; Child ; Child clinical studies ; Children ; Cohort Studies ; Community Health Planning ; DNA ; DNA Methylation ; Environmental aspects ; Epigenesis, Genetic ; Female ; Genes ; Genotyping Techniques ; Gestational Age ; Humans ; Linear Models ; Male ; Medical sciences ; Parturition ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Receptors, Dopamine D4 - genetics ; Serotonin Plasma Membrane Transport Proteins - genetics ; Symptoms ; Trinucleotide Repeat Expansion - genetics</subject><ispartof>Journal of psychiatric research, 2014-02, Vol.49, p.51-59</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c674t-7448aaace4214e7c0092160aadd029a1d57170fd272afe801329e254ec5f4c973</citedby><cites>FETCH-LOGICAL-c674t-7448aaace4214e7c0092160aadd029a1d57170fd272afe801329e254ec5f4c973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpsychires.2013.10.017$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,31009,46004</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28064200$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24290898$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Mil, Nina H</creatorcontrib><creatorcontrib>Steegers-Theunissen, Régine P.M</creatorcontrib><creatorcontrib>Bouwland-Both, Marieke I</creatorcontrib><creatorcontrib>Verbiest, Michael M.P.J</creatorcontrib><creatorcontrib>Rijlaarsdam, Jolien</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Steegers, Eric A.P</creatorcontrib><creatorcontrib>Heijmans, Bastiaan T</creatorcontrib><creatorcontrib>Jaddoe, Vincent W.V</creatorcontrib><creatorcontrib>Verhulst, Frank C</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Eilers, Paul H.C</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>Tiemeier, Henning</creatorcontrib><title>DNA methylation profiles at birth and child ADHD symptoms</title><title>Journal of psychiatric research</title><addtitle>J Psychiatr Res</addtitle><description>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.</description><subject>Attention Deficit Disorder with Hyperactivity - epidemiology</subject><subject>Attention Deficit Disorder with Hyperactivity - physiopathology</subject><subject>Attention deficit disorders. Hyperactivity</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Behavioral Symptoms - etiology</subject><subject>Biological and medical sciences</subject><subject>Birth Order</subject><subject>Birth Weight</subject><subject>Child</subject><subject>Child clinical studies</subject><subject>Children</subject><subject>Cohort Studies</subject><subject>Community Health Planning</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Environmental aspects</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Genes</subject><subject>Genotyping Techniques</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Linear Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Parturition</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Receptors, Dopamine D4 - genetics</subject><subject>Serotonin Plasma Membrane Transport Proteins - genetics</subject><subject>Symptoms</subject><subject>Trinucleotide Repeat Expansion - genetics</subject><issn>0022-3956</issn><issn>1879-1379</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>7QJ</sourceid><recordid>eNqNkk9v1DAQxS1ERZfCV0C5IHHJMmM7cXxBWrpAkar2AJwt15loHfJnsbOV8u3raBcqcdqTJfs3857nDWMZwhoBy4_tut3H2e18oLjmgCJdrwHVC7bCSukchdIv2QqA81zoorxkr2NsAUBxlK_YJZdcQ6WrFdPbu03W07SbOzv5ccj2YWx8RzGzU_bgw7TL7FBnSaqrs832ZpvFud9PYx_fsIvGdpHens4r9uvrl5_XN_nt_bfv15vb3JVKTrmSsrLWOpJJmpQD0BxLsLaugWuLdaFQQVNzxW1DVfoL18QLSa5opNNKXLEPx77J2Z8Dxcn0PjrqOjvQeIgGC4m6QiX5GaiQFQoU8gwUk33U6gwDUqe5SikxodURdWGMMVBj9sH3NswGwSzJmdY8J2eW5JaXlFwqfXdSOTz0VP8r_BtVAt6fABud7ZpgB-fjM1dBKTlA4j4fOUqhPHoKJjpPg6M6abrJ1KM_x82n_5q4zg8-6f6mmWI7HsKQQjdoIjdgfiybtiwaiuQgDVk8AUibzWU</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>van Mil, Nina H</creator><creator>Steegers-Theunissen, Régine P.M</creator><creator>Bouwland-Both, Marieke I</creator><creator>Verbiest, Michael M.P.J</creator><creator>Rijlaarsdam, Jolien</creator><creator>Hofman, Albert</creator><creator>Steegers, Eric A.P</creator><creator>Heijmans, Bastiaan T</creator><creator>Jaddoe, Vincent W.V</creator><creator>Verhulst, Frank C</creator><creator>Stolk, Lisette</creator><creator>Eilers, Paul H.C</creator><creator>Uitterlinden, André G</creator><creator>Tiemeier, Henning</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>7TM</scope><scope>7QJ</scope></search><sort><creationdate>20140201</creationdate><title>DNA methylation profiles at birth and child ADHD symptoms</title><author>van Mil, Nina H ; Steegers-Theunissen, Régine P.M ; Bouwland-Both, Marieke I ; Verbiest, Michael M.P.J ; Rijlaarsdam, Jolien ; Hofman, Albert ; Steegers, Eric A.P ; Heijmans, Bastiaan T ; Jaddoe, Vincent W.V ; Verhulst, Frank C ; Stolk, Lisette ; Eilers, Paul H.C ; Uitterlinden, André G ; Tiemeier, Henning</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c674t-7448aaace4214e7c0092160aadd029a1d57170fd272afe801329e254ec5f4c973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Attention Deficit Disorder with Hyperactivity - epidemiology</topic><topic>Attention Deficit Disorder with Hyperactivity - physiopathology</topic><topic>Attention deficit disorders. Hyperactivity</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Behavioral Symptoms - etiology</topic><topic>Biological and medical sciences</topic><topic>Birth Order</topic><topic>Birth Weight</topic><topic>Child</topic><topic>Child clinical studies</topic><topic>Children</topic><topic>Cohort Studies</topic><topic>Community Health Planning</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Environmental aspects</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Genes</topic><topic>Genotyping Techniques</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Linear Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Parturition</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. 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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.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>24290898</pmid><doi>10.1016/j.jpsychires.2013.10.017</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Attention Deficit Disorder with Hyperactivity - epidemiology Attention Deficit Disorder with Hyperactivity - physiopathology Attention deficit disorders. Hyperactivity Attention deficit hyperactivity disorder Behavioral Symptoms - etiology Biological and medical sciences Birth Order Birth Weight Child Child clinical studies Children Cohort Studies Community Health Planning DNA DNA Methylation Environmental aspects Epigenesis, Genetic Female Genes Genotyping Techniques Gestational Age Humans Linear Models Male Medical sciences Parturition Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Dopamine D4 - genetics Serotonin Plasma Membrane Transport Proteins - genetics Symptoms Trinucleotide Repeat Expansion - genetics |
| title | DNA methylation profiles at birth and child ADHD symptoms |
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