Evidence for multiple loci from a genome scan of autism kindreds

Department of Psychiatry,University of Pittsburgh, Pittsburgh, PA, USAWe performed a genome-wide linkage scan using highly polymorphic microsatellite markers.To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis ofautism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16cM) onchromosome 7q at a location coincident with other linkage studies. When a more relaxeddiagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). Thesample was stratified into families with only male affected subjects (MO) and families with atleast one female affected subject (FC). The strongest signal unique to the MO group was onchromosome 11 (P=0.0009, 83.82cM), and for the FC group on chromosome 4 (P=0.002,111.41cM). We also divided the sample into regression positive and regression negativefamilies. The regression-positive group showed modest linkage signals on chromosomes 10(P=0.003, 0cM) and 14 (P=0.005, 104.2cM). More significant peaks were seen in the regressionnegative group on chromosomes 3 (P=0.0002, 140.06cM) and 4 (P=0.0005, 111.41cM). Finally,we used language acquisition data as a quantitative trait in our linkage analysis and observeda chromosome 9 signal (149.01cM) of P=0.00006 and an empirical P-value of 0.0008 at thesame location. Our work provides strong conformation for an autism locus on 7q andsuggestive evidence for several other chromosomal locations. Diagnostic specificity anddetailed analysis of the autism phenotype is critical for identifying autism loci.Molecular Psychiatry advance online publication, 1 August 2006; doi:10.1038/sj.mp.4001874Keywords: autism; autism spectrum disorder; linkage; genome scan; chromosome 7