Gene × sex interactions on cognition in the philadelphia neurodevelopmental cohort

Abstract Background Small differences between females and males in cognitive abilities have been consistently reported, but the factors underlying these sex differences remain unclear. Social and cultural factors are thought to play a key role, but studies on this topic have been inconclusive. Examination of genetic factors may shed some light on the mechanisms underlying cognitive sex differences. Methods Using data from the Philadelphia Neurodevelopmental Cohort, a large, general population sample of individuals aged 8 to 21 years old (N = 4,694), we tested for sex differences in the genetic factors (i.e., Gene × Sex interactions) underlying cognitive ability. Participants completed the Penn Computerized Neurocognitive Battery, which consists of 14 tests designed to capture accuracy and speed in five domains: 1) executive function (abstraction and mental flexibility, attention, working memory), 2) episodic memory (verbal, facial, spatial), 3) complex cognition (verbal reasoning, nonverbal reasoning, spatial processing), 4) social cognition (emotion identification, emotion differentiation, age differentiation), and 5) speed (motor, sensorimotor). Composite domain scores were derived using confirmatory factor analysis, and general accuracy (g) and speed (gs) using principal component analysis. Results Small sex differences were observed on most cognitive measures (standardized mean difference (SMD) = 0.061–0.182). Males showed significantly higher genetic variance and lower environmental variance in executive (female σ 2 g = 0.301 v. male σ 2 g = 0.598, p = 0.001, female σ 2 e = 0.243 v. male σ 2 e = 0.024, p = 0.007), and complex (female σ 2 g = 0.291 v. male σ 2 g = 0.610, p = 0.001, female σ 2 e = 0.259 v. male σ 2 e = 0.023, p = 0.006) accuracy. Females showed significantly higher genetic and lower environmental variance on complex (female σ 2 g = 0.575 v. male σ 2 g = 0.135, p = 0.009, female σ 2 e = 0.222 v. male σ 2 e = 0.641, p = 0.012) and social (female σ 2 g = 0.589 v. male σ 2 g = 0.129, p = 0.009, female σ 2 e = 0.236 v. male σ 2 e = 0.672, p = 0.012) speed. Genetic correlations between females and males were not significantly different from 1 on any cognitive measure. Altogether, our results suggest that while the same genetic factors influence cognition in females and males, the magnitude of effect of these genetic factors differs. Conclusions We observed small differences between females and males on most cognitive measures, as well as sex differences in heritability on some measures. Future studies are needed to delineate how environmental, genetic, and other biological factors jointly influence cognition.