Although population substructure does not cause type I error in family-based association tests, multiple founder effects could result in reduced power to detect an association in a heterogeneous disease such as autism. Thus we conducted EIGENSTRAT (Patterson, Price & Reich 2006) analysis on all parents from analyzed families for evidence of population substructure using the 491,664 SNPs genotyped in both the discovery and validation datasets. To ensure the most homogeneous groups for association screening and replication, we excluded all families with outliers defined by EIGENSTRAT (Patterson, Price & Reich 2006) out of 4 standard deviations of principle components 1 and 2. After all QC steps, 1,390 samples from 438 autistic families were remained in the final discovery dataset and 2,390 samples from 457 autistic families (supplemental table 1 and 3) in the validation dataset. The average genotyping rate in the remaining individuals was 99.8 %.
