Genome-wide association scan of attention deficit hyperactivity disorder (In special issue: Special Issue on the Genetics of ADHD Dedicated to the Memory of Richard Todd)

Neale, Benjamin M., Lasky-Su, Jessica, Anney, Richard, Franke, Barbara, Zhou, Kaixin, Maller, Julian B., Arias-Vasquez, Alejandro, Asherson, Philip, Chen, Wai, Banaschewski, Tobias, Buitelaar, Jan, Ebstein, Richard, Gill, Michael, Miranda, Ana, Oades, Robert D., Roeyers, Herbert, Rothenberger, Aribert, Sergeant, Joseph, Steinhausen, Hans Christoph, Sonuga-Barke, Edmund, Mulas, Fernando, Taylor, Eric, Laird, Nan, Lange, Christoph, Daly, Mark and Faraone, Stephen V. (2008) Genome-wide association scan of attention deficit hyperactivity disorder (In special issue: Special Issue on the Genetics of ADHD Dedicated to the Memory of Richard Todd). American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 147B (8), 1337-1344. (doi:10.1002/ajmg.b.30866).

Abstract

Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

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