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      Genetics of attention deficit hyperactivity disorder

      review-article
        1 , , 2 , 3
      Molecular Psychiatry
      Nature Publishing Group UK
      Genetics, Neuroscience

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          Abstract

          Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD’s high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD’s heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD’s heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.

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          Most cited references134

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          Molecular genetics of attention-deficit/hyperactivity disorder.

          Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin studies, which estimate the heritability of ADHD to be .76. Molecular genetic studies suggest that the genetic architecture of ADHD is complex. The few genome-wide scans conducted thus far are not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the eight genes for which the same variant has been studied in three or more case-control or family-based studies, seven show statistically significant evidence of association with ADHD on the basis of the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and SNAP-25.
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            Candidate gene studies of ADHD: a meta-analytic review.

            Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.
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              Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study.

              Attention deficit hyperactivity disorder (ADHD) is a common mental disorder associated with factors that are likely to increase mortality, such as oppositional defiant disorder or conduct disorder, criminality, accidents, and substance misuse. However, whether ADHD itself is associated with increased mortality remains unknown. We aimed to assess ADHD-related mortality in a large cohort of Danish individuals.
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                Author and article information

                Contributors
                +315-464-3113 , sfaraone@childpsychresearch.org
                Journal
                Mol Psychiatry
                Mol. Psychiatry
                Molecular Psychiatry
                Nature Publishing Group UK (London )
                1359-4184
                1476-5578
                11 June 2018
                11 June 2018
                2019
                : 24
                : 4
                : 562-575
                Affiliations
                [1 ]ISNI 0000 0000 9159 4457, GRID grid.411023.5, Departments of Psychiatry and of Neuroscience and Physiology, , SUNY Upstate Medical University, ; Syracuse, NY 13210 USA
                [2 ]ISNI 0000 0001 0738 8966, GRID grid.15895.30, School of Medical Sciences, , Örebro University, ; Örebro, Sweden
                [3 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0002-9217-3982
                Article
                70
                10.1038/s41380-018-0070-0
                6477889
                29892054
                0f2aec98-dfb7-4367-9706-acff7232a570
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 August 2017
                : 31 January 2018
                : 19 February 2018
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2019

                Molecular medicine
                genetics,neuroscience
                Molecular medicine
                genetics, neuroscience

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