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Default-mode network (DMN) is a key functional network of the human brain. In this study, we conducted genome-wide association analysis to find regions of the genome linked to variation in the functional activity of the DMN, and we examined whether human-accelerated genes (HAR genes) were specifically enriched in the observed genome regions. The fMRI amplitude of the ICA-based resting-state network resembling the DMN (described as NETMAT amplitudes 25(01) in http://big.stats.ox.ac.uk; UK Biobank field ID: 25754) was taken as the phenotype of interest. GWAS analysis revealed 2 associated genomic loci and 12 genes to be related to variations in DMN amplitude. Using MAGMA linear-regression-based gene-set analysis, we found that the set of brain-expressed HAR genes to be significantly associated with the phenotypic variation in DMN amplitude. Taking the normalized DMN amplitude (corrected for the mean amplitude across all networks) as the phenotype of interest showed similar results. Our findings thus suggest that genetic changes in recent human brain evolution may play a role in the neural activity of the DMN to support increasing human cognitive properties.