A high density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies replicated linkage regions on chromosomes 9 and 16
As part of the International Multi-centre ADHD Gene (IMAGE) project we have completed an affected sibling pair study of 142 narrowly defined DSM-IV combined type ADHD proband-sibling pairs. We found suggestive linkage on chromosomes 9 and 16 with non-parametric multipoint peak LOD scores of 2.13 and 3.1 respectively. There have been several previous ADHD linkage scans. The UCLA study (Fisher et al. 2002; Ogdie et al. 2004; Ogdie et al. 2003), the Dutch study (Bakker et al. 2003), the German study (Hebebrand et al. 2006) and the MGH Study (Faraone et al., submitted) applied the affected sib pair (ASP) strategy; the Columbian study used extended pedigrees ascertained from a population isolate (Arcos-Burgos et al. 2004). No linkage was observed on the most established ADHD linked genomic regions from these studies on 5p and 17p. The highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (LOD=3.1) overlapped with data published from UCLA (LOD>1, ~95cM) and Holland (LOD>1, ~100cM). The second highest peak in this study was on chromosome 9q22 at 90cM (LOD=2.13). Both the UCLA study and the German study also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93cM; German LOD=0.68 at 100cM). The overlap of the two main peaks from this study with those from previous studies suggests that true loci linked to ADHD may lie within these regions.