Fig. 5: Genes pleiotropically associated with schizophrenia and regional MRI metrics.

A Scatterplot of T scores (x-axis) versus U scores (y-axis) for each of 18,640 protein-coding genes, derived from their PLS1 weights (Fig. 2). The T score is the weight of each gene on the MRI metric; the U score is the weight of each gene on the association with schizophrenia; and the correlation between T and U scores, R(T, U), quantifies the strength of genetic relationship between brain and schizophrenia phenotypes. Each gene is colour-coded according to its value of Δ(R(T, U)) which indicates the positive (red) or negative (blue) magnitude of its influence on the whole genome relationship between schizophrenia and each MRI metric. The top ten genes with the largest positive leave-one-out scores for Δ(R(T, U)) are annotated, including PLEKHM1, FMNL1, LRRC37A, MAPT, KANSL and CRHR1, all located within the 17q21.31 region. We note that these genes were also identified by the intersection analysis of genes significantly associated with both MRI metrics and schizophrenia (Fig. 1). B Significant positional enrichment of 185 genes (top 1%) with the highest Δ(R(T, U)) scores based on hypergeometric testing implemented in FUMA. For example, the genes most strongly contributing to genetic covariation between SA and schizophrenia were positionally enriched at chromosome 2q33, whereas genes contributing to covariation between CT and schizophrenia were enriched at chromosome 14q32. The red bars show the proportion of co-located genes according to the size of each gene-set; the blue bars indicate -log10 P-values adjusted for the number of tested gene-sets. Chromosomal locations showing significant local genetic correlations based on LAVA are highlighted in green boxes. C Scatterplot of T scores versus U scores, exactly as shown in (A) except that genes are colour-coded according to their location in the three genomic regions that were positionally enriched for all MRI metrics. Source data are provided as a Source Data file.