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IMAGE - Mapping susceptibility genes for attention deficity hyperactivity disorder

(Funded by Medical Research Council)
Philip Asherson Click Here, Eric Taylor and others

This collaborative project led by Philip Asherson and Eric Taylor brings together expertise from both within the Centre and the Child Psychiatry Unit (Ian Craig, Thalia Eley, Robert Plomin, and Emily Simonoff (UMDS)). Pump-priming funds were made available through the MRC small grant scheme. The aim of this project is to identify genes conferring susceptibility to attention deficit hyperactivity disorder (ADHD) in children. It is now generally accepted that allelic association studies are the most powerful method for detecting genes of small effect in complex disorders and we propose to perform both a systematic genome screen for association and candidate gene association studies. We will apply a novel adaptation of DNA pooling techniques which makes it possible to perform a rapid preliminary genome wide screen for allelic association using 3500 microsatellite markers. The study design will use a multi-stage strategy that balances the risks of false positives and false negatives in the detection of genes of small effect. In parallel with this work we will look for associations with functionally significant variations (FSVs) of candidate genes for ADHD (e.g. DAT1, DRD4, SNAP-25), as well as focusing on genes lying within candidate regions identified by systematic mapping studies in human and syntenic regions from animal models. Gene effects are expected to be small, requiring large and reliably ascertained samples for their detection. We therefore propose to collect 900 probands and matched controls, as well as parental samples to avoid the problem of ethnic stratification in case-control studies. Proband assessments will allow a polydiagnostic approach to be gathered on parental phenotypes, siblings and environmental variables, enabling gene- environment interactions to be studied once genetic risk factors are isolated.

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