Perspective on the genetics of attention deficit/hyperactivity disorder (original) (raw)
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The genetics of ADHD: A literature review of 2005
Current Psychiatry Reports, 2006
Investigations into the genetic basis of attention-deficit/ hyperactivity disorder (ADHD) continue to yield compelling results as candidate gene studies reveal more information about this elusive disorder. Family, twin, and adoption studies further the notion that ADHD is a highly heritable disorder with direct genetic and environmental influence. The year 2005 saw many ADHD candidate gene studies, with most focused on the catecholaminergic candidates. Although many genes were studied in 2005, a large portion of findings has been supportive of the roles of dopaminergic genes’ relationship to clinical phenotypes and drug response. These studies often require replication. Clinical implications continue to be speculative, as larger sample sizes are needed to validate findings to the general population. Further understanding of endophenotypes and the impact of comorbidities also is necessary for proper clinical intervention. Forthwith, we provide a summary of ADHD genetic studies published in 2005.
Genetics of Attention Deficit Hyperactivity Disorder (ADHD): Recent Updates and Future Prospects
Attention deficit hyperactivity disorder (ADHD) is not only highly prevalent, persistent and impairing but also is one of the most heritable of all psychiatric disorders. As a result, ADHD has been the focus of considerable genetic research. The results of recent genetic studies are reviewed with a focus on the emerging picture and future trends. ADHD appears to be a complex disorder in which multiple genetic and environmental risks contribute to a quantitative trait. At the same time, there is growing evidence that in a proportion of cases, individually rare variants such as copy number variants may play an important causal role. The more genetic risks, both common and rare, the more extreme the trait. With increasing samples and advanced genetic methods, single nucleotide polymorphism (SNPs) and copy number variants (CNVs) conferring risk for ADHD are being identified. Further study will be required before we can understand the causal significance of these findings. Increased sample size is an urgent necessity if we are to discover potentially causal variants. Non-behavioral markers of genetic risk known as endophenotypes could also play a role in parsing the phenotypic and genetic heterogeneity of ADHD as they have in other complex disorders. Genetic studies in ADHD hold the potential for refined nosology, more precise diagnosis, and differential diagnosis, improved early identification leading to novel intervention strategies and identification of innovative targets for therapeutics based on a precise understanding of disease mechanism.
Genetics of attention-deficit hyperactivity disorder (ADHD)
Attention-deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous syndrome which is comorbid with childhood conduct disorder, alcoholism, substance abuse, dis-social personality disorder, and affective disorders. A small but consistent overlap with autistic symptoms has also been established. Twin and family studies of ADHD show a substantial genetic heritability with little or no family environmental effect. Linkage and association studies have conclusively implicated the dopamine transporter gene (DAT1). DAT1 has also been confirmed as being associated with bipolar disorder. Remarkably, and for the first time in psychiatry, genetic markers at the DAT1 locus appear to be able to predict clinical heterogeneity because the non-conduct disordered subgroup of ADHD is associated with DAT1 whereas other subgroups do not appear to be associated. The second most well replicated susceptibility gene encodes the DRD4 dopamine receptor and many other dopamine related genes appear to be implicated. It is becoming increasingly clear that genes causing bipolar mania overlap with genes for a subtype of ADHD. The key to understanding the genetics of ADHD is to accept very considerable heterogeneity with different genes having effects in different families and in different individuals. It is too early to interpret the new wave of genome-wide association and copy number variant studies but preliminary data support the overlap with affective disorder genes and also with CNS connectivity genes likely to be involved in autism and affective disorders.
Recent genetic advances in ADHD and diagnostic and therapeutic prospects..pdf
Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder of a complex nature. Genetic and environmental factors are thought to be involved in precipitating the disorder. Pharmacological, animal model and recent molecular studies support the role of genes (of minor or medium effect) from dopamine, serotonin and norepinephrine neurotransmitter systems in ADHD. Several investigations have pointed to the dopamine transporter, the dopamine receptors D4 and D5 and the serotonin transporter as genes of minor effect for ADHD. In addition, recent molecular analysis have also implicated synaptosomal-associated protein-25 and the serotonin receptor 5-Hydroxtryptamine 1B as potential susceptibility loci for ADHD. An understanding of the genetics of ADHD will further facilitate refinement and validation of the ADHD diagnosis, and the development of reliable disease markers in the prediction of disease risk. A knowledge of genes that determine treatment response has the potential to be of predictive value and may also assist in rationalizing drug treatment in the ADHD population. However, increased understanding of inheritance brings its own challenges in the interpretation of new knowledge and in its wise and ethical use, especially in relation to future screening of at-risk individuals. This article attempts to review recent genetic advances and their possible implications for improved diagnosis and treatment.
Case-control genome-wide association study of attention-deficit/hyperactivity disorder
2010
Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genomewide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genomewide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1.
Mini-review on the Basic Genetic Aspects for the Attention Deficit Hyperactivity Disorder (ADHD)
Bulletin of Integrative Psychiatry
Attention deficit hyperactivity disorder (ADHD) is a common and generally inherited neuropsychiatric disorder that is present in children and adults, and it is considered a multifactorial disorder. Due to the limited effects of genes on the manifestation of the disorder, we wanted to analyze the impact of the genes SNAP25, BAIAP2, ANKK1, DAT1 on attention deficit hyperactivity disorder (ADHD) and to emphasize the importance of genetic architecture in the learning experience and the development of an individual since genes can negatively affect an individual's life. Another rationale for this study was the very well-known problem of accurately diagnosing ADHD because this is usually made through questionnaires or interviews with the patient suspected of having the disorder, which can lead to errors. The idea of genetic testing to identify the different polymorphisms of genes responsible for ADHD would make the diagnosis more accurate. As a result, we searched the databases for articles in which the authors reported the impact of the genes mentioned above. We identified a total of 12 relevant articles that were discussed throughout this article. We concluded that all the genes selected for this study were implicated in the manifestation of this disorder, only when a specific circumstance was met such as a specific ethnic group was tested, or a specific polymorphism was studied.
Journal of Neural Transmission, 2008
A genome-wide association (GWA) study with pooled DNA in adult attention-deficit/hyperactivity disorder (ADHD) employing ~500K SNP markers identifies novel risk genes and reveals remarkable overlap with findings from recent GWA scans in substance use disorders. Comparison with results from our previously reported high-resolution linkage scan in extended pedigrees confirms several chromosomal loci, including 16q23.1-24.3 which also reached genome-wide significance in a recent meta-analysis of seven linkage studies (Zhou et al. in Am J Med Genet Part B, 2008). The findings provide additional support for a common effect of genes coding for cell adhesion molecules (e.g., CDH13, ASTN2) and regulators of synaptic plasticity (e.g., CTNNA2, KALRN) despite the complex multifactorial etiologies of adult ADHD and addiction vulnerability.
Advances in genetic studies of attention-deficit/hyperactivity disorder
Current Psychiatry Reports, 2009
Attention-defi cit/hyperactivity disorder (ADHD) is among the most common childhood-onset psychiatric disorders. Although family, twin, and adoption studies demonstrate that ADHD is a highly heritable condition, studies also suggest that genetic architecture is complex, prompting the use of more advanced methodologies such as genome-wide linkage and association studies. Although such studies are theoretically compelling, replication of these results has been inconsistent. Meta-analyses have produced more reliable results, but the associations identifi ed to date account for only a small percentage of the genetic component of ADHD. Approaches such as neuroimaging genetics and epigenetic studies are being explored to probe further the etiologic complexity of this disorder.