A connection-level genetic atlas of human cortical functional connectivity at rest and during a task

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 ε4 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.