Identifying susceptibility genes for Attention Deficit Hyperactivity Disorder with antisocial behaviour as a covariate. (360G-Wellcome-079711_Z_06_Z)

Attention Deficit Hyperactivity Disorder (ADHD) is a common, neurodevelopmental childhood-onset disorder that has life-long adverse consequences. ADHD is highly heritable but the pathogenesis of the disorder remains unknown. Identifying susceptibility genes and examining how these, together with environmental factors, influence ADHD is extremely important if novel, effective methods of prevention and therapeutic intervention are to be developed. ADHD is commonly accompanied by antisocial behavio ur that is not only a major public health and societal problem itself but also indexes greater clinical severity, a poorer outcome, greater persistence in adult life and higher familiality and genetic loading of ADHD. The aims of this proposal are to identify genes that increase susceptibility for ADHD, have effects on associated antisocial behaviour and that have effects which are conditional on exposure to environmental risk factors. The study design is a traditional genetics approach that is enhanced by evidence from clinical and epidemiological studies. Specifically the design is a whole-genome SNP-based linkage study of a UK sample of affected sib pairs followed up by linkage disequilibrium mapping. The search is refined by using covariate-based linkage analysis with antisocial behaviour as the clinical covariate and including environmental factors that are robustly associated with ADHD.