Fig. 2: Comparisons of genetic architecture and polygenic overlap across the two sexes.
From: Sex-stratified genome-wide association meta-analysis of major depressive disorder
a Autosomal SNP-based heritability (hSNP) on the liability scale using a population prevalence of 0.1 in males and 0.2 in females, b Polygenicity, and (c) Selection parameter. d Autosomal SNP-based genetic correlation (rg) between males and females using our sex-stratified meta-analysis results, and meta-analysis of rg estimated in all six male-female within cohort, 30 male-female across cohort, 15 male-male across cohort and 15 female-female across cohort combinations. e Pearson correlation of the Major Depressive Disorder (MDD) effect sizes of SNPs known to be associated with sex-combined MDD for males vs females using our sex-stratified meta-analysis results, and meta-analysis of Pearson correlations estimated in all six male-female within cohort, 30 male-female across cohort, 15 male-male across cohort and 15 female-female across cohort combinations. f Venn diagram depicting the number of causal variants explaining 90% of MDD h2SNP in females only, males only, or both sexes, as identified by MiXeR. g Venn diagram depicting the number of genomic regions that contain a causal variant for MDD in females only, males only or both sexes, as identified by gwas-pw. Females or female-female comparisons are in yellow, males or male-male comparisons in dark purple and female-male comparisons in green. For a–c a Bayesian framework was used. Estimates were obtained using SBayesS with summary statistics from the sex-stratified GWAS meta-analysis (females: 130,471 cases and 159,521 controls; males: 64,805 cases and 132,185 controls). Violin plots display the posterior distributions, points represent the mean posterior value, error bars are the 95% highest posterior density interval and percentages are the posterior probability that female value > male value. For d and e frequentist statistics were used. Background points represent individual values from each study included in the meta-analysis, and overlaid points and error bars represent the mean estimate and 95% confidence interval from the meta-analysis. Stars represent the rg / R being significantly different to 1, based on a two-sided Z-test with p values adjusted for five comparisons using the Benjamini-Hochberg method. Exact p-values are provided in the Results section.
