Elsevier

Biological Psychiatry

Volume 57, Issue 11, 1 June 2005, Pages 1313-1323
Biological Psychiatry

Advancing the neuroscience of ADHD
Molecular Genetics of Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1016/j.biopsych.2004.11.024Get rights and content

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.

Section snippets

Family, Twin, and Adoption Studies of ADHD

Several studies have reported an elevated prevalence of ADHD among family members of individuals with ADHD (here and elsewhere we use the term “ADHD” to refer to current and prior terms used to describe the syndrome). Early studies found the risk of ADHD among parents of children with ADHD to be increased by two- to eightfold, with similarly elevated risk among the siblings of ADHD subjects (for a review of this literature, see Faraone and Biederman 2000). Because other environmental

Molecular Genetic Studies of ADHD

In an attempt to find regions of chromosomes that might harbor genes for ADHD, three groups have conducted genome-wide linkage scans. By this approach, many DNA acid markers across the genome are examined to determine whether any chromosomal regions are shared more often than expected among ADHD family members. Regions identified in these studies can then be examined in more detail with additional markers.

A study of 126 American affected sib-pairs found four regions showing some evidence of

Discussion

Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. The handful of genome-wide scans that have been conducted thus far show divergent findings and are, therefore, not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. As Table 1 shows, for the eight genes for which the same variant

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