Fig. 6: Specificity of pleiotropic associations between clinical disorders or height and regional brain phenotypes.

A Proportion of variance in the genetically predicted risk for each disorder and height (y-axis) explained by the genetic effects on regional MRI metrics (x-axis; SA surface area, CT cortical thickness, NDI neurite density index) based on the first PLS component, PLS1. B Cortical surface maps of PLS1 regional brain weights for schizophrenia (SCZ), BIP, AD and height. Higher positive weights (shades of yellow) indicate stronger genetic covariation with each disorder; regions with zero weight are shown in white. Mean absolute weights were lower for BIP (SA \(\bar{w}\) = 12.3, CT \(\bar{w}\) = 9.45, NDI \(\bar{w}\) = 8), and for AD (SA\(\bar{w}\) = 9, CT \(\bar{w}\) = 5.2, NDI \(\bar{w}\) = 5.4), than for schizophrenia (SA \(\bar{w}\) = 18.29, CT \(\bar{w}\) = 11.89, NDI \(\bar{w}\) = 11.37). Apart from SA, mean PLS weights for height were generally lower than for schizophrenia (SA\(\bar{w}\) = 20.4, CT \(\bar{w}\) = 12.1, NDI \(\bar{w}\) = 10.5). Fewer brain regions had significant PLS1 scores for BIP (NDI = 175) and AD (SA = 79, CT = 166, NDI = 170) than for schizophrenia (SA, CT = 180, NDI = 179). For height, all brain regions showed significant PLS1 scores. C Spearman’s correlations (ρ; y-axis) between T and U scores for schizophrenia, bipolar disorder, Alzheimer’s disease and height. The strength of pleiotropic association indexed by ρ was greater for schizophrenia (SA ρ = 0.24, CT ρ = 0.23, NDI ρ = 0.17), than for BIP (SA ρ = 0.17, CT ρ = 0.19, NDI ρ = 0.13), AD (SA ρ = 0.12, CT ρ = 0.11, NDI ρ = 0.09). For SA, the pleiotropic association with height was stronger compared to schizophrenia (SA ρ = 0.27, CT ρ = 0.23, NDI ρ = 0.16). D Venn diagrams showing the intersection of the top 1% most pleiotropic genes, with the highest Δ(R(T, U)) scores, for each MRI metric. Source data are provided as a Source Data file.