Associations between brain imaging–derived phenotypes and cognitive functions

Abstract We aimed to evaluate the potential causal relationship between brain imaging–derived phenotypes and cognitive functions via Mendelian randomization analyses. Genetic instruments for 470 brain imaging–derived phenotypes were selected from a genome-wide association study based on the UK Biobank (n = 33,224). Statistics for cognitive functions were obtained from the genome-wide association study based on the UK Biobank. We used the inverse variance weighted Mendelian randomization method to investigate the associations between brain imaging–derived phenotypes and cognitive functions, and reverse Mendelian randomization analyses were performed for significant brain imaging–derived phenotypes to examine the reverse causation for the identified associations. We identified three brain imaging–derived phenotypes to be associated with verbal–numerical reasoning, including cortical surface area of the left fusiform gyrus (beta, 0.18 [95% confidence interval, 0.11 to 0.25], P = 4.74 × 10−7), cortical surface area of the right superior temporal gyrus (beta, 0.25 [95% confidence interval, 0.15 to 0.35], P = 6.30 × 10−7), and orientation dispersion in the left superior longitudinal fasciculus (beta, 0.14 [95% confidence interval, 0.09 to 0.20], P = 8.37 × 10−7). The reverse Mendelian randomization analysis indicated that verbal–numerical reasoning had no effect on these three brain imaging–derived phenotypes. This Mendelian randomization study identified cortical surface area of the left fusiform gyrus, cortical surface area of the right superior temporal gyrus, and orientation dispersion in the left superior longitudinal fasciculus as predictors of verbal–numerical reasoning.