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bioRxiv · 10.1101/2025.08.27.672637

Lifestyle and transcriptional signatures associated with ethnicity/race-related variations in the functional connectome

Han, Z.·Wang, K.·Liu, T.·Ma, Y.·Yang, G.·Yan, T.
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Abstract

Understanding the variation of functional architecture across individuals and populations is fundamental to advancing our knowledge of human health and behaviour. Yet, while functional organization differences related to ethnicity/race are consistently reported, their underlying mechanisms remain poorly understood. Here, we apply precision individualized functional mapping to systematically investigate ethnicity/race-related differences in the brains intrinsic organization and their associations with lifestyle and transcriptional signatures. We show that variations in network topography and functional connectivity across ethnic/racial groups follow a hierarchical sensorimotor- association axis and are constrained by brain morphology. Importantly, we identify lifestyle factors-- particularly education and substance use--that significantly mediate these associations between ethnicity/race and functional connectivity. Leveraging human brain gene expression data, we further demonstrate that cortical transcriptional patterns are spatially aligned with ethnicity/race-related variability in functional connectivity. Gene ontology analyses of associated genes reveal significant enrichment in biological processes such as synaptic signalling and neuronal system development. Together, these findings uncover a multi-layered framework linking ethnicity/race-related differences in brain function to structural constraints, lifestyle influences, and molecular signatures, and advance a more comprehensive and equitable understanding of human brain diversity.

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Han, Z., Wang, K., Liu, T., Ma, Y., Yang, G., Yan, T.. 2025-09-01. Lifestyle and transcriptional signatures associated with ethnicity/race-related variations in the functional connectome. https://doi.org/10.1101/2025.08.27.672637

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