Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is typically characterized by inattention, excessive motor activity, impulsivity, and distractibility. Individuals with ADHD have significant impairment in family and peer relations, academic functioning, and show high co-morbidity with a wide range of psychiatric disorders including oppositional defiant disorder (ODD), conduct disorder (CD), anxiety disorder, depression, substance abuse, and pervasive developmental disorder (PDD). Family studies suggest that ADHD + CD represents a specific subtype of the ADHD disorder with familial risk factors only partly overlapping with those of ADHD alone. We performed a hypothesis-free analysis of the GAIN-ADHD sample to identify markers and genes important in the development of conduct problems in a European cohort of individuals with ADHD. Using the Family-Based Association Test (FBAT) package we examined three measures of conduct problems in 1,043,963 autosomal markers. This study is part of a series of exploratory analyses to identify candidate genes that may be important in ADHD and ADHD-related traits, such as conduct problems. We did not find genome-wide statistical significance (P < 5 x 10(-7)) for any of the tested markers and the three conduct problem traits. Fifty-four markers reached strong GWA signals (P < 10(-5)). We discuss these findings in the context of putative candidate genes and the implications of these findings in the understanding of the etiology of ADHD + CD. We aimed to achieve insight into the genetic etiology of a trait using a hypothesis-free study design and were able to identify a number of biologically interesting markers and genes for follow-up studies.