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DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study
The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothes...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877354/ https://www.ncbi.nlm.nih.gov/pubmed/24391992 http://dx.doi.org/10.1371/journal.pone.0085164 |
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author | Tovo-Rodrigues, Luciana Rohde, Luis A. Menezes, Ana M. B. Polanczyk, Guilherme V. Kieling, Christian Genro, Julia P. Anselmi, Luciana Hutz, Mara H. |
author_facet | Tovo-Rodrigues, Luciana Rohde, Luis A. Menezes, Ana M. B. Polanczyk, Guilherme V. Kieling, Christian Genro, Julia P. Anselmi, Luciana Hutz, Mara H. |
author_sort | Tovo-Rodrigues, Luciana |
collection | PubMed |
description | The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothesize that genetic heterogeneity in the VNTR is an important factor in the pathophysiology of ADHD. The subjects included in the present study are members of the 1993 Pelotas Birth Cohort Study (N=5,249). We conducted an association study with the 4,101 subjects who had DNA samples collected. The hyperactivity-inattention scores were assessed through the parent version of the Strengths and Difficulties Questionnaire at 11 and 15 years of age. The contribution of allele’s length and rare variants to high hyperactivity/inattention scores predisposition was evaluated by multivariate logistic regression. No effect of allele length was observed on high scores of hyperactivity-inattention. By contrast, when resequencing/haplotyping was conducted in a subsample, all 7R rare variants as well as non-synonymous 7R rare variants were associated with high hyperactivity/inattention scores (OR=2.561; P=0.024 and OR=3.216; P=0.008 respectively). A trend for association was observed with 4R rare variants. New coding mutations covered 10 novel motifs and many of them are previously unreported deletions leading to different stop codons. Our findings suggest a contribution of DRD4 7R rare variants to high hyperactivity-inattention scores in a population-based sample from a large birth cohort. These findings provide further evidence for an effect of DRD4 7R rare variants and allelic heterogeneity in ADHD genetic susceptibility. |
format | Online Article Text |
id | pubmed-3877354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38773542014-01-03 DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study Tovo-Rodrigues, Luciana Rohde, Luis A. Menezes, Ana M. B. Polanczyk, Guilherme V. Kieling, Christian Genro, Julia P. Anselmi, Luciana Hutz, Mara H. PLoS One Research Article The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothesize that genetic heterogeneity in the VNTR is an important factor in the pathophysiology of ADHD. The subjects included in the present study are members of the 1993 Pelotas Birth Cohort Study (N=5,249). We conducted an association study with the 4,101 subjects who had DNA samples collected. The hyperactivity-inattention scores were assessed through the parent version of the Strengths and Difficulties Questionnaire at 11 and 15 years of age. The contribution of allele’s length and rare variants to high hyperactivity/inattention scores predisposition was evaluated by multivariate logistic regression. No effect of allele length was observed on high scores of hyperactivity-inattention. By contrast, when resequencing/haplotyping was conducted in a subsample, all 7R rare variants as well as non-synonymous 7R rare variants were associated with high hyperactivity/inattention scores (OR=2.561; P=0.024 and OR=3.216; P=0.008 respectively). A trend for association was observed with 4R rare variants. New coding mutations covered 10 novel motifs and many of them are previously unreported deletions leading to different stop codons. Our findings suggest a contribution of DRD4 7R rare variants to high hyperactivity-inattention scores in a population-based sample from a large birth cohort. These findings provide further evidence for an effect of DRD4 7R rare variants and allelic heterogeneity in ADHD genetic susceptibility. Public Library of Science 2013-12-31 /pmc/articles/PMC3877354/ /pubmed/24391992 http://dx.doi.org/10.1371/journal.pone.0085164 Text en © 2013 Tovo-Rodrigues et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Tovo-Rodrigues, Luciana Rohde, Luis A. Menezes, Ana M. B. Polanczyk, Guilherme V. Kieling, Christian Genro, Julia P. Anselmi, Luciana Hutz, Mara H. DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title | DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title_full | DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title_fullStr | DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title_full_unstemmed | DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title_short | DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study |
title_sort | drd4 rare variants in attention-deficit/hyperactivity disorder (adhd): further evidence from a birth cohort study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877354/ https://www.ncbi.nlm.nih.gov/pubmed/24391992 http://dx.doi.org/10.1371/journal.pone.0085164 |
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