Educational attainment was among the traits showing strong negative genetic correlation with depression (Supplementary Table S5A). To further evaluate the impact of depression genetic risk on cognition, we analyzed the association of depression polygenic scores (DEP-PRS) with 15 cognitive measures in the Philadelphia Neurodevelopmental Cohort (PNC, N=4,973)66,67. Cognitive performance was measured by the Computerized Neurocognitive Battery68, including 14 tests in 5 domains: executive-control, episodic memory, complex cognitive processing, social cognition, and sensorimotor speed. In addition, the Wide Range Achievement Test (WRAT-4)69 was used as a proxy measure for overall IQ67. The depression-PRS was negatively associated with abstraction and mental flexibility (β=−0.039, SE=0.014, FDR=0.030, Figure 4, Supplementary Table S12A). Applying a narrower definition of depression (see Methods, Supplementary Table S13 and Figure S14) yielded moderately stronger negative associations, with attention, abstraction, and mental flexibility in the executive-control domain, and verbal reasoning in the reasoning domain surpassing statistical significance (Figure 4, Supplementary Table S12B). These results are consistent with observational studies reporting that individuals with depression display lower performance in cognitive domains such as executive function, memory, language and attention70-72, and demonstrate
