The ADHD Genetic Group
THE ADHD GENETIC GROUP
The ADHD Genetic Group a research group within the SGDP whose main aim is to identify the genes involved in ADHD and related behavioural traits, and investigate how such genes work together and with environment to influence behaviour. For further information on any of these projects please contact Lena Johansson (Professor Phil Asherson’s office).
MAPPING GENES FOR ADHD – INTRODUCTION
ADHD, hyperactivity and related problems are very common, affecting the lives of many children and adults. The disorder is recognised as one of the most important cause of problems that some children have with their schoolwork and relationships with friends and family. These problems often have long-term consequences so that about two thirds of children diagnosed with ADHD have persistent problems that effect them as adults. By investigating the causes and finding out much more about how genes and environments – nature and nurture – combine together to bring about ADHD, we will be in a far better position to develop the best and most effective approaches to help individuals with ADHD. Finding the genes involved in an important step in this direction since we know that genetic influences on ADHD are particularly important.
Molecular genetic methods have been highly successful in identifying genes of major effect that co-segregate with single gene disorders. As a result huge strides have been made in our understanding of conditions such as Huntington’s Disease, fragile-X syndrome, familial Alzheimer’s disease and rare familial epilepsies, among many others. Progress in identifying genetic risk factors for more common and complex disorders has however proved to be far more difficult since in most cases the genetic influences result from multiple genetic variants, each conferring only a small additional risk to disease susceptibility. This is the case for attention deficit hyperactivity disorder (ADHD) where familial risks are relatively low, with an estimated sibling risk ratio (risk to siblings of ADHD probands/population risk) for broadly defined ADHD of around 3-4 fold.
Twin studies support the view that genetic factors are the major influence on familial risk with heritability estimates for ADHD symptom scores consistently reported to be in the region of 60-90%. These studies find no role for shared environmental influences on familiarity, although the role of environment may still be pivotal acting through mechanisms of gene-environment interaction. Progress in identifying some of the genes involved in ADHD susceptibility has been relatively fruitful over the past decade by screening genetic variants that lie within or close to genes that regulate neurotransmitter systems, particularly dopamine pathways. The genes that have already been identified as risk factors for ADHD include the dopamine D4 receptor gene (DRD4), the dopamine transporter gene (DAT1), the dopamine D5 receptor gene (DRD5) and synaptosomal associated protein (SNAP-25). It is important to note that all of these genes confer only a small additional risk to ADHD on their own (odds ratio range from 1.2 – 2).
Other strategies using genetic linkage designs to screen the entire human genome have been less successful to date but hold the promise of identifying novel gene systems that could lead to major advances in our knowledge of ADHD etiology. These studies have less power to detect genes of small effect such as those already identified, but could identify important genes with a greater influence on risk for ADHD.