Abstract
White matter (WM) connections support efficient interregional communication and form the structural basis of human fluid intelligence. However, the shared genetic architecture between WM structural connectome and fluid intelligence remains largely unknown. In this study, we analyzed diffusion-weighted MRI data from 26,655 UK Biobank participants to construct individual WM connectome and performed genome-wide association analyses on global and regional network topology. We identified 41 single nucleotide polymorphisms (SNPs) significantly associated with global efficiency and 45 SNPs linked to nodal efficiency. Genetic correlations with fluid intelligence were observed for 128 brain regions, with 44 and 3 regions sharing SNPs within chromosomes 6q21 and 3p21.1, respectively. Mendelian randomization revealed causal effects from WM connectome to fluid intelligence, particularly in the orbital and superior frontal gyrus. Finally, integrating polygenic scores with network efficiency improved the prediction of individual fluid intelligence. These findings highlight the genetic basis linking WM connectome topology and fluid intelligence, providing new insights into the neurogenetic underpinnings of fluid intelligence.
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Acknowledgements
This research has been conducted using the UK Biobank Resource under Application Number 49749 and was partially supported by High Performance Computing Platform of Nanjing University of Aeronautics and Astronautics. This work was supported by the Brain Science and Brain-like Intelligence Technology - National Science and Technology Major Project (2022ZD0213300, 2021ZD0200500), National Natural Science Foundation of China (82301608, 32271145, 81871425), Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning (CNLZD2303), Beijing Natural Science Foundation (L252087).
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Dong, X., Huang, W., Chen, HJ. et al. Shared genetic architecture between the topology of brain white matter structural connectome and fluid intelligence. Commun Biol (2026). https://doi.org/10.1038/s42003-026-10131-0
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DOI: https://doi.org/10.1038/s42003-026-10131-0
