Chunk #19 — Using Results from the GWAS of the International Schizophrenia Consortium as an Example, Are the Results of Dickson et al. Supported by Empirical Observation?
Schizophrenia is a common complex disease for which several studies [8],[9],[10],[11] (including one by the ISC) have identified a role for very rare structural variants in its underlying genetic architecture. In a GWAS comprising of 3,322 cases and 3,587 controls [12], the ISC analysis presented evidence that some common genetic variants also contribute to the genetic architecture, demonstrated by the highly significant signal of association of in an independent case-control sample based on a profile of the top 50% of associated SNPs from the ISC study. In the ISC study we undertook simulations of a wide range of genetic architectures in which we varied allele frequency, effect size distributions and the extent of LD between causal and genotyped SNPs. Although we could reject many of the simulated genetic architectures as not being representative of the observed results, many others were consistent with our results, but all consistent models included common variants as well as rare causal variants. Dickson et al. cites the ISC paper and specifically implied that multiple rare variants could explain the ISC results. Since our only conclusion
