Our study identified a novel association between intronic SNP rs16856199 and rMDD in hospital-referral subjects. Segregation with diagnosis in the relatives of these probands corroborated the association, but further studies are required to understand the lack of replication in population-based cohorts with depression. This may be due to inherent differences between patients recruited from hospital-referral compared with those from population-based cohorts. Cohorts from primary care are more likely to have a family history of depression,75 and may have more physical and psychiatric comorbidity in general. Conversely, the population-based sample may have shorter, less severe episodes76 than the hospital-based cohorts.77 However, given the modestly significant P-value for rMDD in the discovery cohort, the number of psychiatric traits examined and the lack of replication, it is possible that the observed association is due to chance.
