Background. Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. Method. Multivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). Results. Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=x0.25 to x0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. Conclusions. The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD. ; PUBLISHED ; PMID:20522277 ; This work was supported in part by National Institutes of Health (NIH) grants R01MH62873 and R01MH081803 to S. V. Faraone and, in London, by a UK Medical Research Council grant G03001896 to J. Kuntsi. We thank all the families who kindly participated in this research. Principal investigators for this study were P. Asherson, T. Banaschewski, S. V. Faraone, M. Gill, J. Kuntsi, I. Manor, A. Miranda, F. Mulas, R. D. Oades, A. Rothenberger, H. Royers and H.-C. Steinhausen. The analyses were performed by A. C. Wood and F. Rijsdijk, who were also part of the writing group with J. Kuntsi, P. Asherson, K. Johnson and S. V. Faraone. B. Albrecht, P. Andreou, H. Christiansen and H. Uebel were further investigators at data collection sites. J. van der Meere contributed the go/no-go task and was involved in the review of the draft. A. Arias-Vasquez, J. Buitelaar, G. McLoughlin, N. Rommelse, J. Sergeant and E. Sonuga-Barke were involved in reviewing and discussing the data. We thank further team members at data collection sites of Dublin, Essen, Ghent, Go¨ttingen, London, Tel Aviv, Valencia and Zurich for their important contributions.