ORIGINAL PAPER A Study of how Socioeconomic Status Moderates the Relationship between SNPs Encompassing BDNF and ADHD Symptom Counts in ADHD Families J. Lasky-Su Æ Stephen V. Faraone Æ C. Lange Æ M. T. Tsuang Æ A. E. Doyle Æ J. W. Smoller Æ N. M. Laird Æ J. Biederman Received: 12 May 2006 / Accepted: 20 November 2006 / Published online: 10 January 2007 Ó Springer Science+Business Media, LLC 2007 Abstract Recent animal research suggests that brain- derived neurotrophic factor (BDNF), may mediate response to different environmental stimuli. In this paper, we evaluated the possible role of BDNF as a moderator of attention deficit hyperactivity disorder (ADHD) in the context of different socioeconomic classes. We genotyped ten single nucleotide polymor- phisms (SNPs) in and around BDNF in 229 families and evaluate whether there are SNP-by-socioeco- nomic status (SES) interactions for attention deficit hyperactivity. We developed three quantitative phe- notypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that were used in SNP-by-SES interaction analyses using a new meth- odology implemented in the computer program PBAT. Findings were adjusted for multiple compar- isons using the false discovery rate. We found multiple significant SNP-by-SES interactions using the inattentive symptom count. This study suggests that different SES classes may modify the effect of the functional variant(s) in and around BDNF to have an impact on the number of ADHD symptom counts that are observed. The two exons within BDNF represent potential functional variants that may be causing the observed associations. Keywords Gene-by-environment interaction  BDNF  ADHD  SES  Family-based association test  PBAT Background Accumulating evidence suggests attention deficit hyperactivity disorder (ADHD) is a complex disorder with both genetic and environmental causes. Family, twin, and adoption studies show the etiology of ADHD is influenced by genes. Family studies show that relatives of ADHD individuals have higher rates of ADHD compared with relatives of controls (Bieder- man et al. 1992; Cantwell 1972; Doyle et al. 2001; Faraone et al. 1993, 1994; Morrison and Stewart 1971; Welner et al. 1977). Additional lines of evidence from twin and adoption studies suggest this familial trans- mission is, in part, due to genes, with higher concor- dance rates for ADHD found in monozygotic twins Edited by Stacey Cherny J. Lasky-Su  S. V. Faraone (&) Medical Genetics Research Program, Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA e-mail: faraones@upstate.edu C. Lange  N. M. Laird Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA M. T. Tsuang Department of Psychiatry, Institute of Behavioral Genomics, University of California, San Diego, CA, USA A. E. Doyle  J. Biederman Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA, USA J. W. Smoller Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA Behav Genet (2007) 37:487–497 DOI 10.1007/s10519-006-9136-x 123