Fig. 3.
Spatial coupling between human gray matter volume sex differences and expression of sex-chromosome genes. (A) Schematic of method used to rank genes based on the spatial coupling of brain expression with unthresholded regional sex differences (male-female) in cortical GMV. (B) Schematic showing how relative gene ranking relates to the relationship between gene expression and GMV sex biases. Bold borders denote genes within a set of interest (e.g., sex-linked genes), and the asterisk indicates the median rank for this gene set upon which inferences are made. The polarity of gene rankings is set so that more negative ranks indicate more positive correlation between gene expression and the t-statistic of GMV in males vs. females. This ranking positions sex-linked genes first in a “left-right” reading of C. (C) Point-range plot of the median rank (marked by circle with SD as error bar) of genes on the sex chromosomes and each autosome. Sex chromosomes (X- and Y-linked) genes uniquely showed a statistically significant extreme median rank (relative to the middle line/zero rank, Prand = 0.0014, all chromosome ranks given in SI Appendix, Table S7). The polarity of this rank extremity indicates a positive spatial correlation (marked in red) between sex-chromosome gene expression and male-female differences in GMV (i.e., relative high expression where GMV is greater in males than females and relatively low expression where GMV is greater in females than males). (D) Scatter plot of expression for X- and Y-linked genes ranked at the top 5% of SI Appendix, Table S6 (i.e., those with most extremely positive correlations with the t-statistic map of male-female GMV) vs. their aligned t-values of GMV sex differences (see details in Materials and Methods).