Homo sapiens Exome. Homo sapiens

Treatment-resistant depression (TRD) is a severe form of major depressive disorder (MDD) with substantial public health impact and poor treatment outcome. Treatment outcome in MDD is significantly heritable, but genome-wide association studies have failed to identify replicable common marker alleles, suggesting a potential role for uncommon variants. Here we investigated the hypothesis that uncommon, putatively functional genetic variants are associated with TRD. Whole-exome sequencing data was obtained from 182 TRD cases. These data were compared to those obtained from 2,021 psychiatrically healthy controls. After quality control, the remaining 149 TRD cases and 1,976 controls were analyzed with tests designed to detect excess burdens of uncommon variants.