The genetic landscape of heterogeneity in human functional brain connectivity

Understanding the genetic underpinnings of functional brain connectivity is essential to understand its role in brain health and disease. A mass-univariate approach was adopted to investigate the genetic architecture of functional brain circuitry (UKB, ntotal = 28,159 subjects), showing common genetic variants in 33% of all 3,321 interregional functional pathways. Seventy-two locus-connection associations with widespread (pleiotropic) effects throughout the brain were found and mapped to five protein-coding genes: PAX8, EphA3, SLC39A12, THBS1 and APOE. Functional annotation of these genes revealed converged in biological processes related to neurodevelopment, alongside with significant overlap with phenotypes in cardiovascular and cognitive phenotypes domains (enrichment minimum p = 3.0{middle dot}10-6 and p = 1.6{middle dot}10-5, respectively). Our findings show a genetic component of interindividual differences in functional brain connectivity that is shared with traits related to cognitive function and overall health.