Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children
The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD...
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description | The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample. |
doi_str_mv | 10.1038/sj.mp.4000744 |
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J</creator><creatorcontrib>TAHIR, E ; YAZGAN, Y ; CIRAKOGLU, B ; OZBAY, F ; WALDMAN, I ; ASHERSON, P. J</creatorcontrib><description>The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4000744</identifier><identifier>PMID: 10889550</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Alleles ; Attention Deficit Disorder with Hyperactivity - drug therapy ; Attention Deficit Disorder with Hyperactivity - genetics ; Attention deficit disorders. 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J</creatorcontrib><title>Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><description>The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.</description><subject>Alleles</subject><subject>Attention Deficit Disorder with Hyperactivity - drug therapy</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>Attention deficit disorders. 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Hyperactivity</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child clinical studies</topic><topic>Children</topic><topic>Cognitive ability</topic><topic>DNA nucleotidylexotransferase</topic><topic>Dopamine</topic><topic>Dopamine D4 receptors</topic><topic>Dopamine D5 receptors</topic><topic>Dopamine receptors</topic><topic>Dopamine Uptake Inhibitors - administration & dosage</topic><topic>Family Health</topic><topic>Genes</topic><topic>Genetic factors</topic><topic>Genetic Linkage</topic><topic>Humans</topic><topic>Hyperactivity</topic><topic>Impulsive behavior</topic><topic>Impulsivity</topic><topic>Logistic Models</topic><topic>Medical sciences</topic><topic>Methylphenidate</topic><topic>Methylphenidate - administration & dosage</topic><topic>Polymorphism, Genetic</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Receptors, Dopamine D1 - genetics</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D4</topic><topic>Receptors, Dopamine D5</topic><topic>Synapses</topic><topic>Treatment Outcome</topic><topic>Turkey</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TAHIR, E</creatorcontrib><creatorcontrib>YAZGAN, Y</creatorcontrib><creatorcontrib>CIRAKOGLU, B</creatorcontrib><creatorcontrib>OZBAY, F</creatorcontrib><creatorcontrib>WALDMAN, I</creatorcontrib><creatorcontrib>ASHERSON, P. 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J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children</atitle><jtitle>Molecular psychiatry</jtitle><addtitle>Mol Psychiatry</addtitle><date>2000-07-01</date><risdate>2000</risdate><volume>5</volume><issue>4</issue><spage>396</spage><epage>404</epage><pages>396-404</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>10889550</pmid><doi>10.1038/sj.mp.4000744</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alleles Attention Deficit Disorder with Hyperactivity - drug therapy Attention Deficit Disorder with Hyperactivity - genetics Attention deficit disorders. Hyperactivity Attention deficit hyperactivity disorder Biological and medical sciences Child Child clinical studies Children Cognitive ability DNA nucleotidylexotransferase Dopamine Dopamine D4 receptors Dopamine D5 receptors Dopamine receptors Dopamine Uptake Inhibitors - administration & dosage Family Health Genes Genetic factors Genetic Linkage Humans Hyperactivity Impulsive behavior Impulsivity Logistic Models Medical sciences Methylphenidate Methylphenidate - administration & dosage Polymorphism, Genetic Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Dopamine D1 - genetics Receptors, Dopamine D2 - genetics Receptors, Dopamine D4 Receptors, Dopamine D5 Synapses Treatment Outcome Turkey |
title | Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children |
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