Family-Based Genome-Wide Association Scan of AD/HD.

Abstract

Objective : Genes likely play a substantial role in the etiology of AD/HD. However, the genetic architecture of the disorder in unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD. Method : families were ascertained at Massachusetts General Hospital (MGN ; N=309 trios), Washington University at St Louis (WAS-U ; N= 272 trios), and Unifersity of California at Los Angeles (UCLA ; N=156 trios). Genotyping was conducted with the Illumina Human1M or Human 1M-Duo BeadChip platforms. After applying quality control filters, association with ADHD was tested with 835,136 SNPs in 735 DSM-IV ADHD trios from 732 families. Results : our smallest p value (6.7E-07) did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, p=6.4E-6). We also conducted gene-based tests of candidate fenes identified in the litterature and found additional evidence of association with SLC9A9. Conclusions : we and our colleague in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders.