Brain Structure and Function Show Distinct Relations with Genetic Predispositions to Mental Health and Cognition

BACKGROUND: Mental health and cognitive achievement are partly heritable, highly polygenic, and associated with brain variations in structure and function. However, the underlying neural mechanisms remain unclear.METHODS: We investigated the association between genetic predispositions to various mental health and cognitive traits and a large set of structural and functional brain measures from the UK Biobank (N = 36,799). We also applied linkage disequilibrium score regression to estimate the genetic correlations between various traits and brain mea-sures based on genome-wide data. To decompose the complex association patterns, we performed a multivariate partial least squares model of the genetic and imaging modalities.RESULTS: The univariate analyses showed that certain traits were related to brain structure (significant genetic correlations with total cortical surface area from rg =-0.101 for smoking initiation to rg = 0.230 for cognitive ability), while other traits were related to brain function (significant genetic correlations with functional connectivity from rg =-0.161 for educational attainment to rg = 0.318 for schizophrenia). The multivariate analysis showed that genetic predispositions to attention-deficit/hyperactivity disorder, smoking initiation, and cognitive traits had stronger associations with brain structure than with brain function, whereas genetic predispositions to most other psychiatric disorders had stronger associations with brain function than with brain structure.CONCLUSIONS: These results reveal that genetic predispositions to mental health and cognitive traits have distinct brain profiles.