A connection-level genetic atlas of human cortical functional connectivity at rest and during a task
- 1University of North Carolina at Chapel Hill
Abstract
Genetic studies of cortical functional connectivity have analyzed aggregated traits, which fails to show which connections a variant acts on. We present a connection-level genetic atlas: genome-wide association analyses of 64,620 connections among 360 cortical areas in UK Biobank participants of European ancestry at rest (n = 52,983) and during an emotion-processing task (n = 45,010), with replication in an independent sample (n = 15,546). We identified 247 resting and 96 task loci; 193 resting loci were new to fMRI genetics and 112 replicated. Most loci affected connections between networks. Colocalization linked APOE {varepsilon}4 to lowered posterior default mode connectivity and a cognition locus to left posterior temporal (PHT) connections; the right PHT was a replicated hub. Genes near the loci included 155 drug targets, 50 with psychiatric indications and 15 targeted by approved psychiatric drugs. Resting connectivity was more heritable and colocalized more often with complex traits than task connectivity, whereas task connectivity was more strongly associated with circulating metabolites. The atlas provides summary statistics for every connection in two brain states.
Related
- Migraine-related differences in connectivity patterns during emotional audiovisual processing revealed by functional connectivity multivariate pattern analysis.
- Cerebellar stimulation modulates working memory performance and anterior cerebellum-thalamic-cortical network connectivity in a subgroup of individuals with early course psychosis
- Sex-Modulated Coupling Between Genetically-Regulated Gene Expression and Functional Network Connectivity in Schizophrenia
- Impact of circadian rhythm disruptions on the emotional brain: gray matter and functional connectivity changes in the amygdala
- Frontoparietal functional connectivity underlies top-down attention in mild cognitive impairment
BibTeX
@misc{wu2026connectionlevel,
title = {{A connection-level genetic atlas of human cortical functional connectivity at rest and during a task}},
author = {S. Wu and B. Zhao and Z. Jiang and A. Hara and Z. Sun and X. Li and Z. Zhang and X. Qi and I. Pan and Y. Cheng and Y. Jiang and B. Tang and S. Huang and S. Gao and S. Liu and S. Yu and Y. Zhou and P. Guan and M. Hu and Y. Deng and Y. Li and J. Stein and P. F. Sullivan and T. Li and h. zhu},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.26366764},
url = {https://www.medrxiv.org/content/10.64898/2026.10.28.26366764v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A connection-level genetic atlas of human cortical functional connectivity at rest and during a task
AU - S. Wu
AU - B. Zhao
AU - Z. Jiang
AU - A. Hara
AU - Z. Sun
AU - X. Li
AU - Z. Zhang
AU - X. Qi
AU - I. Pan
AU - Y. Cheng
AU - Y. Jiang
AU - B. Tang
AU - S. Huang
AU - S. Gao
AU - S. Liu
AU - S. Yu
AU - Y. Zhou
AU - P. Guan
AU - M. Hu
AU - Y. Deng
AU - Y. Li
AU - J. Stein
AU - P. F. Sullivan
AU - T. Li
AU - h. zhu
PY - 2026
DA - 2026/10/28
PB - medRxiv
DO - 10.64898/2026.10.28.26366764
UR - https://www.medrxiv.org/content/10.64898/2026.10.28.26366764v1
AB - Genetic studies of cortical functional connectivity have analyzed aggregated traits, which fails to show which connections a variant acts on. We present a connection-level genetic atlas: genome-wide association analyses of 64,620 connections among 360 cortical areas in UK Biobank participants of European ancestry at rest (n = 52,983) and during an emotion-processing task (n = 45,010), with replication in an independent sample (n = 15,546). We identified 247 resting and 96 task loci; 193 resting loci were new to fMRI genetics and 112 replicated. Most loci affected connections between networks. Colocalization linked APOE {varepsilon}4 to lowered posterior default mode connectivity and a cognition locus to left posterior temporal (PHT) connections; the right PHT was a replicated hub. Genes near the loci included 155 drug targets, 50 with psychiatric indications and 15 targeted by approved psychiatric drugs. Resting connectivity was more heritable and colocalized more often with complex traits than task connectivity, whereas task connectivity was more strongly associated with circulating metabolites. The atlas provides summary statistics for every connection in two brain states.
ER -