Heritability and genetic contribution analysis of structural-functional coupling in human brain

Abstract

The flow of functional connectivity (FC) is thought to be supported by white matter structural connectivity (SC). While research on the correlations between SC and FC (SC-FC coupling) has progressed, the genetic implications of SC-FC coupling have not been thoroughly examined. Traditionally, SC-FC coupling investigations utilize predefined atlases. Here, we adopted an atlas-free SC-FC coupling built on the high-resolution white surface (the interface of white matter and gray matter) to uncover common genetic variations. Leveraging data from the Human Connectome Project, we demonstrated considerable heritability in areas within the early and intermediate visual cortex and across dorsal-attention, language, and somatomotor functional networks. We detected 334 genetic loci (spanning 234 cytogenetic bands) linked to SC-FC coupling (P < 1.26 × 10−11), notably in cingulo-opercular, somatomotor, and default mode networks. Using an external dataset from the Adolescent Brain Cognitive Development study, we confirmed 187 cytogenetic bands associated with SC-FC coupling across 22 brain regions (P < 1× 10-5). Genetic correlation analyses revealed high genetic interrelatedness for SC-FC coupling in neighboring regions. Furthermore, it showed genetic correlations with a spectrum of complex traits, encompassing various neurological and psychiatric conditions. In essence, our study paves the way towards deciphering the genetic interplay between structural and functional connectivity of the brain.