We judged the intersection of this GWAS result with prior knowledge sufficient to trigger a large-scale replication effort by genotyping PCLO SNPs in 6,079 MDD independent cases and 5,893 controls. Statistical power to replicate exceeded 90% even after accounting for (79) the “Winner's Curse” phenomenon (a form of regression to the mean whereby the true genotypic relative risk is over-estimated in the initial study) (91, 92). However, in spite of the apparent a priori strength of a hypothesis of genetic variation in PCLO in the etiology of MDD, no SNP analyzed in the replication sample met appropriately rigorous criteria for replication (21). Therefore, unlike GWAS for many non-psychiatric biomedical disorders, our GWAS and replication efforts did not yield “proof beyond a reasonable doubt” level of evidence for an association between genetic variation in PCLO and MDD.
