Genome-wide linkage in Utah autism pedigrees

Genetic studies of autism over the past decade suggest a complex landscape of multiple genes. In the face of this heterogeneity, studies that include large extended pedigrees may offer valuable insight, as the relatively few susceptibility genes within single large families may be more easily discerned. This genome-wide screen of 70 families includes 20 large extended pedigrees of 6–9 generations, 6 moderate-sized families of 4–5 generations, and 44 smaller families of 2–3 generations. The Center for Inherited Disease Research (CIDR) provided genotyping using the Illumina Linkage Panel 12, a 6K single nucleotide polymorphism (SNP) platform. Results from 192 subjects with an Autism Spectrum Disorder (ASD), and 461 of their relatives revealed genome-wide significance on chromosome 15q, with three possibly distinct peaks: 15q13.1-q14 (HLOD=4.09 at 29,459,872bp); 15q14-q21.1 (HLOD=3.59 at 36,837,208bp); and 15q21.1-q22.2 (HLOD=5.31 at 55,629,733bp). Two of these peaks replicate previous findings. There were additional suggestive results on chromosomes 2p25.3-p24.1 (HLOD=1.87), 7q31.31-q32.3 (HLOD=1.97), and 13q12.11-q12.3 (HLOD=1.93). Affected subjects in families supporting the linkage peaks found in this study did not reveal strong evidence for distinct phenotypic subgroups.