In conclusion, we estimate that about one quarter of variation in liability to schizophrenia, or approximately one third of genetic variation in liability, is tagged when considering all genotyped and imputed SNP simultaneously. The remaining ‘missing’ heritability most likely reflects imperfect LD between causal variants and the genotyped and imputed SNPs. The current generation of genotyping chips may explain only ~70% of the total variance attributable to common SNPs (MAF > 0.1) and explains less of variance attributable to uncommon and rare variants (Supplementary Figure 1). From the analyses we have performed we cannot estimate a frequency distribution of the allele frequency of causal variants, but the most likely cause of low LD between causal variants and SNPs is that many causal variants have low MAF. Nevertheless, from the results presented we can conclude that common causal variants in LD with genotyped and imputed SNPs must contribute to genetic variation for liability to schizophrenia in the population. Hence, causal risk variants for schizophrenia range across the entire “allelic spectrum”.
