Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a genetic etiology of the disorder, although putative alleles, principally in dopamine-related pathways suggested by candidate-gene studies, have very small effect sizes. We use affected-sib-pair analysis in 203 families to localize the first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13 (maximum LOD score 4.2; P=.000005), building upon an earlier genomewide scan of this disorder. The region overlaps that highlighted in three genome scans for autism, a disorder in which inattention and hyperactivity are common, and physically maps to a 7-Mb region on 16p13. These findings suggest that variations in a gene on 16p13 may contribute to common deficits found in both ADHD and autism.

Figure 1

MLSs for ADHD and markers on chromosome 16p. The relative marker locations, estimated in the current data set, are shown by diamonds. The SNPs are shown as a single point, with the average MLS indicated in the figure at that position. The SNP distances were based on physical distances (HGP-sc, August 2001 build) and were ordered as follows (with intermarker distances given, in Mb): rs153783–.005–rs1125972–.02–rs1065838–.05–rs1127293–.005–rs1107143.