Genome-Wide Association Study of the Child Behavior Checklist Dysregulation Profile

Objective: : A potentially useful tool for understanding the distribution and determinants of emotional dysregulation in children is a Child Behavior Checklist profile, comprising the Attention Problems, Anxious/Depressed, and Aggressive Behavior clinical subscales (CBCL-DP). The CBCL-DP indexes a heritable trait that increases susceptibility for later psychopathology, including severe mood problems and aggressive behavior. We have conducted a genome-wide association study of the CBCL-DP in children with attention-deficit/hyperactivity disorder (ADHD). Method: Families were ascertained at Massachusetts General Hospital and University of California, Los Angeles. Genotyping was conducted with the Illumina Human1M or Human1M-Duo Bead Chip platforms. Genome-wide association analyses were conducted with the MQFAM multivariate extension of PLINK. Results: CBCL data were available for 341 ADHD offspring from 339 ADHD affected trio families from the UCLA (N = 128) and the MGH (N = 213) sites. We found no genome-wide statistically significant associations but identified several plausible candidate genes among findings at p < 5E-05: TMEM132D, LRRC7, SEMA3A, ALK, and STIP1. Conclusions: We found suggestive evidence for developmentally expressed genes operant in hippocampal dependent memory and learning with the CBCL-DP. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(8): 807-817.