Fig. 1. Neuroticism with overall or cognitive decline specific cortical co-expression gene modules.

A The impact of neuroticism on the overall cortical co-expression gene modules. Each dot represents one module and its expected and observed associations with neuroticism (−log10 P values) are shown on X and Y axis, respectively. The expected P values assume a null distribution with no linear associations between neuroticism score and expression level of co-expressed gene module after adjusting age at death, sex, education, race, postmortem interval, study (ROS or MAP), RNA-seq batch and RIN score. The gray and dark areas indicate the extreme ranges of the QQ plot as generated by chance at a threshold of P = 0.05 and P = 0.10, respectively. The 95 and 90% confidence intervals were empirically derived by randomly assigning participants with the neuroticism score and repeating the analysis 1000 times. Based on the distribution of the observed P values for all the 47 co-expressed gene modules, the overall association between neuroticism and module expression was unlikely to have occurred by chance (omnibus P = 0.005). B The impact of neuroticism on the cognitive decline related co-expression gene modules. Each dot represents one module (the module number is listed next to each dot) and their previously reported P values for the cognitive decline⁶ are shown on the Y axis and the P values (−log10 transformed) of the effect of neuroticism are shown on the X axis with the red dashed line for the threshold of P = 0.05. The red dots are those that were previously reported to be associated with cognitive decline⁶. C, D Distribution of cortical module m7 and m127 expression in individuals with different levels of neuroticism. Each dot represents one subject, and the subjects are distributed into three groups based on their neuroticism score: Group 1 with score from 0 to 12; Group 2 with score from 13 to 24; Group 3 with score from 25 to 36. On this scale, scores go from 0 (no neuroticism) to 36 (extensive neuroticism). E Volcano plot of the associations between neuroticism score and mRNA expression level of each of the 499 genes included in the top 4 modules associated with both neuroticism and cognitive decline with color codings of m7 in purple, m6 in blue, m127 in green, and m131 in red. F Volcano plot of the associations between neuroticism score and the 11 previously reported cognitive decline associated co-expressed gene modules with color codings of different cell type: astrocyte in red, cholinergic neuron in green, GABAergic neuron in blue, and other excitatory neuron in purple. For both volcano plots, X axis shows the BETA and Y axis shows the −log10 transformed P values with the red dashed line represents the threshold of P = 0.05.