ASD Samples
The samples were collected as part of the AGP, an international consortium with over 50 sites in North America and Europe. The first phase of the AGP involved examining genetic linkage and chromosomal rearrangements in 1,168 families with at least two ASD-affected individuals.5 In the second phase, we genotyped simplex and multiplex families by using high-resolution microarrays to examine the contribution of rare CNVs and common SNPs to ASD. The second phase was divided in two stages; the results of stage 1, involving the first half of the families, were published in 2010.6,20 In stage 2, we genotyped the remaining families (n = 1,604) for a total of over 2,845 families and performed genome-wide CNV (this study) and association studies.21 Informed consent was obtained from all participants, and all procedures followed were in accordance with the ethical standards on human experimentation of the participating sites. The AGP sample set is a collection of families comprising an affected proband and two parents, as previously described in Pinto et al.6 and Anney et al.20,21 Many of the subjects at the recruiting sites were tested for fragile X syndrome (FXS [MIM 300624]) and assessed for chromosomal rearrangements with karyotype, fluorescence in situ hybridization, or multiplex-ligation-dependent probe amplification (MLPA); subjects with known karyotypic abnormalities, FXS, or other genetic disorders were typically excluded. The main analyses presented here were restricted to subjects of European ancestry.21 All diagnostic, clinical, and cognitive assessments were carried out at each contributing site. All data were gathered at a central coordination site for standardization of data formatting and data quality assurance.