Fig. 4: Diagnoses from physicians relate to measures of brain asymmetry change.

Manhattan plots relate (A) longitudinal brain asymmetry changes (LBACs) and (B) magnitude of brain asymmetry changes (MBACs) across the population to 174 composite disease clusters spread across 17 domains. For each composite disease cluster, two-sided Pearson correlation coefficients are shown in units on a logarithmic scale of the associated P-value. Results from all 33 distinct asymmetry patterns are showcased. Horizontal lines indicate the significance thresholds at FDR labelled FDR, Bonferroni correction (0.05/174) labelled BON, with 5 and 6(LBAC) or 8 and 12 (MBAC) phenotypes passing each respective threshold. Composite disease clusters were constructed either by (i) PCA on 1662 medical diagnosis phecodes from the full UKBB cohort (~ 500,000 individuals) (crosses) (ii) CCA on 1447 medical diagnosis phecodes from the brain imaging UKBB cohort (~ 40,000 individuals) and resting state fMRI (circles), or (iii) PLS-C on 1447 medical diagnosis phecodes from the brain imaging UKBB cohort (~ 40,000 individuals) and resting state fMRI (squares). Inlaid barplots showcase the 6 largest absolute medical diagnoses phecodes which contribute to a composite disease cluster. Text within inlaid graphs indicates the composite disease cluster name and which asymmetry pattern change(s) it was significantly correlated to. Composite disease clusters are named in the format METHOD-DOMAIN-#, where METHOD is a 3-character code for the data compression technique (PCA, CCA, or PLS-C); DOMAIN is a 4 letter code indicating the first 4 characters of the associate disease domain (for example, NEOP indicates neoplasms), and the number indicates the latent-factor component for the corresponding method (for example, PCA components 1 or 2). In short, brain asymmetry changes are consistently related to common physician-diagnosed mental health disorders, including depression, suicidality and anxiety, substance use and sleep disorders. NOS not otherwise specified; CIN Cervical intraepithelial neoplasia. Source data are provided as a Source Data file.