The International Schizophrenia Consortium study showed that the SNPs which failed to reach genome-wide significance included some true genetic risk factors. Firstly, variations across nominally associated loci were summarized into quantitative scores in a discovery case–control study. Aggregate risk scores for individuals in independent case–control samples were then calculated. Score alleles designated in the discovery sample were significantly enriched among replication cases. The International Schizophrenia Consortium also showed that the same “set of score alleles” distinguished bipolar cases from controls, thus providing support for the hypothesis that there is a genetic overlap between schizophrenia and bipolar disorder. Although these SNPs explained only approximately 3% of the variance in schizophrenia risk, this can be regarded as the first molecular genetic evidence in support of the theory of the polygenic inheritance of schizophrenia (International Schizophrenia Consortium, 2009).
