Finally, we note that invoking the biological argument is unnecessary. If statistical significance is marginal or if replication is required, then a more definitive study should be designed and conducted in order to falsify the hypothesis. In many instances, this is achievable via collaboration and may be difficult for rarer genetic variants. We believe that schizophrenia genetics needs secure associations (significant beyond chance with precise replication) in order for genomic knowledge to be used as the essential anchor for understanding the biological basis of schizophrenia. Best practices in 2014 are thus very different from 2004. For example, the AKT1 paper appeared in Nature Genetics in 2004 59 with a considerable amount of biological and mouse model data but the genetic data are a SNP P-value of 0.05 (uncorrected for five genotyped SNPs) with no replication data.
