Genotypic analysis of alternative classifications of attention-deficit/hyperactivity disorder

R. D. Todd, E. Rasmussen, E. Lobos, W. Reich, R. Neuman, A. Heath

Research output: Contribution to journalArticle

Abstract

A fundamental issue in studies aimed at identifying genetic components contributing to risk for Attention-Deficit/ Hyperactivity Disorder (ADHD) is what are the appropriate phenotypes for genetic analyses. Most linkage and association studies utilize DSM-IV criteria. We have developed an alternative ADHD classification based on the clustering of ADHD symptoms in population-based samples of nearly 7,000 twin pairs and siblings from North America and Australia. Using both DSM-IV and latent class analysis defined ADHD phenotypes, the possible involvement of genes in the ventral dopaminergic reward pathway system was investigated by both analyses of known polymorphisms and screening for mutations. Screenings of known polymorphisms for the dopamine D4 receptor gene, the dopamine transporter gene and mutation screenings for the dopamine D2 receptor gene and the neural nicotinic acetylcholine receptor a4 gene have been completed for 523 family trios (an affected individual plus both biological parents). No significant associations were detected for either classification system using family-based control association analyses. The current study offers no support for previously reported associations of DRD4 and DAT polymorphisms with DSM-IV or latent class ADHD phenotypes. No significantly linked variations of coding regions of the DRD2 or the nicotinic acetylcholine receptor a4 genes were identified. Current candidate gene studies cannot reliably distinguish the two-phenotyping approaches.

Original languageEnglish
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume105
Issue number7
StatePublished - Oct 8 2001

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