Shared genomic architecture of the brain white matter structural connectome and intelligence

Abstract

White matter (WM) connections, which facilitate communication between brain regions, substantially impact intellectual performance. However, the shared genetic underpinnings of WM connections and intelligence remain unclear. In the present study, we first conducted genome-wide association studies on the global and regional topological properties of WM connectomes constructed from diffusion-weighted and T1-weighted magnetic resonance images of 26,655 participants from the UK Biobank. Forty-one independent significant single-nucleotide polymorphisms (SNPs) associated with global WM connectome efficiency and 45 SNPs linked to nodal efficiency for 246 brain regions were identified. Then, regional heterogeneity was demonstrated for the genetic correlations between WM connectome efficiency and intelligence. The nodal efficiency of 128 regions with nominally significant genetic correlations with intelligence was determined. Among these, 44 regions and 3 regions shared SNPs with intelligence within the chromosome 6q21 and 3p21.1 locus respectively, and significant causal effects on intelligence were found for 63 regions, mainly in the orbital gyrus and superior frontal gyrus. Finally, we found that the integration of polygenetic score and WM connectome efficiency data was more accurate for predicting individual intelligence than the use of a single data type. These findings improve our understanding of how genes shape the individual WM connectome and intelligence and the relationship between WM connectomes and intelligence.