Genetic markers for depressive disorders with earlier age at onset.

Age at onset has been considered a potential indicator of underlying genetic risk in depression research. However, the variants associated with earlier age at onset of depressive disorder have not been elucidated. To evaluate the genetic architecture of depression onset, whole-exome sequencing of samples from 1000 patients with depressive disorder was performed. Cox proportional hazard models with false discovery rate-adjusted P-values were used to estimate the hazard ratios; carriers and non-carriers of individual coding variants were compared in terms of age at onset of depression with adjustment for sociodemographic and clinical characteristics. The clinical relevance of the candidate variants was also examined. Whole-exome sequencing revealed four variants in the CCL14, FYB, GPRASP1, and CTNND2 genes associated with an increased risk of depressive disorder with earlier age at onset. Although no individual variant was associated with any clinical characteristic except AAO, together they were associated with younger AAO, younger age at visit for treatment, and recurrent and atypical depression. Our data suggest novel candidate genes for depressive disorder with earlier age at onset. These genes could serve as markers allowing early identification of patients at risk of depression, and thus earlier intervention.