The genetic landscape of human functional brain connectivity

Investigating the genetic underpinnings of functional brain connectivity is essential to understand how genetic variation influences brain health and disease. Here, a mass-univariate approach was adopted to study the genetic architecture of functional brain circuitry (N_total = 28,159 subjects) with high spatial resolution (82 brain regions). Common genetic variants explained individual differences in 33% of all 3321 inter-regional functional pathways with 72 significant associations reflecting widespread, pleiotropic effects across the connectome. These associations were mapped to five genes-PAX8, EphA3, SLC39A12, THBS1 and APOE-with known associations with brain phenotypes and which converged in biological processes related to neurodevelopment and cardiovascular and cognitive traits (enrichment minimum p = 3.0 × 10^-6 and p = 1.6 × 10^-5, respectively). Our findings show that the genetic component of individual differences in functional brain connectivity is largely shared throughout the brain, highlighting the importance of genetic variation in large-scale brain organisation and its relationship with cognitive function and overall health.