Fig. 3: Manhattan plot, spatial mapping and PheWAS plot relating to the association between the dMRI ICVF measure and rs67827860 (VCAN).

a, The Manhattan plot relates to the original IDP GWAS with the strongest association (ICVF in the right inferior longitudinal fasciculus using tractography, associated with rs67827860). The ICVF parameter, estimated from the NODDI modelling³⁶, aims to quantify predominantly intra-axonal water in white matter, by estimating where water diffusion is restricted. Summary details of SNP rs67827860 are given in the top right box. The lower grey line indicates the –log₁₀(P value) threshold of 7.5 and the upper line the threshold of 11. b, Spatial mapping of rs67827860 against voxelwise ICVF in white matter (ICVF was averaged across all 4,957 subjects with zero copies of the non-reference allele, and the average from all 2,304 subjects that had one copy was subtracted from that, for display in colour here; the difference was thresholded at 0.005 (unitless fractional measure)). Unlike the examples of (spatially) very focal effects in T2* and grey matter volume in Fig. 2 and Extended Data Fig. 1, the effects of this SNP are extremely widespread across most of the white matter tracts (associated with 45 out of the 199 IDPs in cluster 11, Supplementary Table 5). c, The PheWAS plot for SNP rs67827860 shows the association (−log₁₀(P)) on the y-axis for the SNP with each of the 3,144 IDPs. The IDPs are arranged on the x-axis in the three panels: structural MRI IDPs (top), dMRI IDPs (middle) and fMRI IDPs (bottom). Points are coloured to delineate subgroups of IDPs. Grey lines show the Bonferroni multiple testing threshold of 4.79. In addition to the IDP of white matter hyperintensities volume, there is a notable association with numerous dMRI IDPs (especially diffusion tensor-derived measures of fractional anisotropy, mean diffusivity and L1, L2 and L3 eigenvalues of the diffusion tensor, as well as additional ICVF measures).