The science behind ADHD: Cellular modelling of ADHD risk genes
Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric condition affecting 7.4% of Australian children and adolescents.
Children and adolescents affected by ADHD can experience extreme levels of motor activity, impulsivity and inattention that, in 30-60% of cases, persist into adult life. Furthermore, individuals with ADHD have major impairments in family and peer relations, academic functioning, and are at increased risk for drug abuse.
Genetic influences are recognised as a major predisposing factor for the disorder, with heritability for ADHD estimated between 75-90%. Yet, identifying the individual DNA variations that confer risk to ADHD has been a major scientific challenge over the last 20 years.
Crucially, recent meta-analysis of data arising from genome wide association studies (GWAS) of 20,183 ADHD cases and 35,191 controls by the Psychiatric Genetics Consortium – including studies undertaken at MICCN – identified 12 single nucleotide polymorphisms (SNPs) that meet the stringent statistical standards for genome wide association with ADHD. Put simply, the genetics of ADHD are being unravelled, providing an entrée to its neurobiology in the overall quest for the identification and implementation of effective treatment.
Thanks to the award of a recent NHMRC Project Grant, MICCN’s Dr Ziarih Hawi, NHMRC Early Career Fellow Dr Janette Tong, and Professor Mark Bellgrove can now undertake the next step in the discovery pipeline – that is, to define the molecular mechanism putting people at genetic risk for ADHD. This research will ultimately help to reduce the burden to individuals and society caused by ADHD.
“We will use editing technology to engineer ADHD risk SNPs into neuronal cell lines and assess their functional impact on the genes,” Dr Hawi said. “The state-of-the-art bioinformatics pipeline created by Professor Bellgrove’s team enables us to prioritise probable pathogenic variants, with the next step being to apply CRISPR technology to the prioritised targets. This allows us to develop an in vitro cellular model of pathogenic variants.
I am grateful to the NHMRC for their support. The research will significantly enhance our knowledge of the neurobiology of ADHD and could lead to the identification of new novel targets for pharmacological intervention.”
MICCN congratulates Dr Hawi and the investigator team on their success, and looks forward to reporting the positive impacts of the team’s work.
For more information on Dr Ziarih Hawi’s research, please contact him on t: 03 9905 1498, e: Ziarih.Hawi@monash.edu.