One strategy adopted in GWAS to guard against artifacts from population stratification is to genotype family trio samples (cases and their parents) and then analyze the data as a case-control sample, with controls generated as genomic complements of the cases (pseudo-controls). ADHD subset 1 and most of the ASD sample comprised case-pseudocontrol samples and, consistent with this strategy limiting the impact of artifacts from population stratification or genotyping, it is noted that the lowest SNP-based heritability for the five psychiatric disorders was for ASD and that the estimate of SNP-based heritability was lower for ADHD subset 1 than for ADHD subset 2. However, under a polygenic model, assortative mating41 or preferential ascertainment of multiplex families could diminish the expected mean difference in liability between pseudocontrols and cases37, which would result in an underestimation of SNP-based heritability from case-pseudocontrol compared to case-control analyses and would also result in nonzero estimates of SNP-based heritability from pseudocontrol-control analyses, as shown in analysis of ASD data37.
