reflects not one, but three distinct symptom dimensions (psychomotor/cognitive, mood, and neurovegetative symptoms).148 Thus, GWAS that simply examine “depressed” cases versus controls may decrease the ratio of “signal to noise” by combining multiple disorder subtypes that vary in their genetic etiology. In light of evidence suggesting that there is no truly categorical threshold for depression caseness,149 and that different lifetime prevalence estimates of depression are found when comparing cross-sectional retrospective reports to cumulative evaluations based on multiple interviews,150 it is reasonable to posit that misclassification of individuals as cases or controls may be undermining the power of typical case-control GWAS.
