A genomewide screen for autism susceptibility loci

We report the analysis of 335 microsatellite markers genotyped in 110 multi plex families with autism. All families include at least two "affected" sib lings, at least one of whom has autism; the remaining affected sibs carry d iagnoses of either Asperger syndrome or pervasive developmental disorder. A ffected sib-pair analysis yielded multipoint maximum LOD scores (MLS) that reach the accepted threshold for suggestive linkage on chromosomes 5, X, an d 19. Nominal evidence for linkage (point-wise) was obtained on chromosomes 2, 3, 4, 8, 10, 11, 12, 15, 16, 18, and 20, and secondary loci were found on chromosomes 5 and 19. Analysis of families sharing alleles at the putati ve X chromosomal linked locus and one or more other putative linked loci pr oduced an MLS of 3.56 for the DXS470-D19S174 marker combination. In an effo rt to increase power to detect linkage, scan statistics were used to evalua te the significance of peak LOD scores based on statistical evidence at adj acent marker loci. This analysis yielded impressive evidence for linkage to autism and autism-spectrum disorders with significant genome-wide P values <.05 for markers on chromosomes 5 and 8 and with suggestive linkage eviden ce for a marker on chromosome 19.