Back

The genetic landscape of heterogeneity in human functional brain connectivity

Maciel, B. d. A. P. C.; Schipper, M.; Romero, C.; de Leeuw, C.; Helwegen, K.; Posthuma, D.; Savage, J. E.; van den Heuvel, M.

2025-04-10 genetic and genomic medicine
10.1101/2025.04.08.25325384 medRxiv
Show abstract

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.

Published in Nature Communications (predicted rank #2) · training set

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.