The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. However, the gene Show more
The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. However, the genetic basis linking sociability with DMN function remains underexplored. This study aimed to elucidate the shared genetics and causal relationship between sociability and DMN-related resting-state functional MRI (rs-fMRI) traits. We conducted a comprehensive genomic analysis using large-scale genome-wide association study (GWAS) summary statistics for sociability and 31 activity and 64 connectivity DMN-related rs-fMRI traits ( Significant local genetic correlations were identified between sociability and two rs-fMRI traits, one representing spontaneous activity within the temporal cortex, the other representing connectivity between the cingulate and angular/temporal cortices. MR analyses suggested potential causal effects of sociability on 12 rs-fMRI traits. Seventeen genes were highly prioritized, with By combining genomic and transcriptomic data, our gene prioritization strategy may serve as a blueprint for future studies. Our findings can guide further research into the biological mechanisms underlying sociability and its role in the development, prognosis, and treatment of neuropsychiatric disorders. Show less
The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. In the present st Show more
The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. In the present study, we examined the genetic relationship between sociability and DMN-related resting-state functional magnetic resonance imaging (rs-fMRI) traits. To this end, we used genome-wide association summary statistics for sociability and 31 activity and 64 connectivity DMN-related rs-fMRI traits (N=34,691-342,461). First, we examined global and local genetic correlations between sociability and the rs-fMRI traits. Second, to assess putatively causal relationships between the traits, we conducted bi-directional Mendelian randomisation (MR) analyses. Finally, we prioritised genes influencing both sociability and rs-fMRI traits by combining three methods: gene-expression eQTL MR analyses, the CELLECT framework using single-nucleus RNA-seq data, and network propagation in the context of a protein-protein interaction network. Significant local genetic correlations were found between sociability and two rs-fMRI traits, one representing spontaneous activity within the temporal cortex, the other representing connectivity between the frontal/cingulate and angular/temporal cortices. Sociability affected 12 rs-fMRI traits when allowing for weakly correlated genetic instruments. Combing all three methods for gene prioritisation, we defined 17 highly prioritised genes, with Show less