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Journal Article
The genetic landscape of human functional brain connectivity
2026
Overview
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.
Genetic variation shapes brain-wide patterns of functional networks. This study identifies key genes associated with macroscale functional brain connectivity and links genes and brain activity with cognitive and physical traits.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 59/36
/ 59/57
/ Adult
/ Apolipoproteins E - genetics
/ Biobanks
/ Brain
/ Circuits
/ Female
/ Genes
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Polymorphism, Single Nucleotide
/ Science
