PMC

Schizophrenia-associated SNP heritability estimates of average cortical thickness (a) and surface area (b) measurements of 35 anatomical traits that are significantly heritable. Eight cortical structural traits that show significantly enriched contribution of the schizophrenia-associated SNPs at an FDR of 0.1 are labeled.

Estimates of SNP heritability explained by independently ascertained schizophrenia-associated SNPs compared to the null expectation. The disease-associated SNP selection procedure is as follows: all genotyped SNPs were ranked based on the results of the recent genome-wide case/control association study of schizophrenia, obtained from the Psychiatric Genomics Consortium. Based on the rank, disease-associated SNPs were selected to consist of 10% of the genotyped SNPs in our dataset, and the remaining 90% of SNPs were assigned as non-associated SNPs. GCTA was used to perform a joint analysis of two set-based genetic components. The y-axis represents 35 brain anatomical traits separated into three groups: (1) global anatomical measures; (2) cortical thickness; and (3) surface area measurements. The x-axis represents estimated schizophrenia-set-based SNP heritability for a respective trait. Estimated heritability is displayed by a solid navy-color bar, while the null expectation (i.e., estimates calculated based on the proportion of SNPs with respect to genome-wide SNP heritability) is shown by a dashed gray-line bar. Error bars represent the standard errors of the estimates. Significance of enrichment was calculated using a Monte-Carlo simulation. Brain traits with enriched schizophrenia-set-based heritability at FDR q ≤ 0.1 are highlighted with asterisk (*** uncorrected p<0.001; ** p <0.01; * p<0.05).

Enrichment analysis results for various disorder-associated SNP-set-based heritability. We examined seven disorders: (1) SCZ: schizophrenia; (2) ADHD: attention deficit hyperactivity disorder; (3) AUT: autism spectrum disorder; (4) AN: anorexia nervosa; (5) BIP: bipolar disorder; (6) MDD: major depressive disorder; and (7) CD: Crohn’s disease. For each disorder, the results of publicly available genome-wide case/control association study were obtained from the Psychiatric Genomics Consortium and used to rank genotype SNPs based on the significance of disease-association. The x-axis represents five SNP set selection thresholds: top 10%, 20%, 30%, 40%, and 50%. For each of the SNP selection thresholds, we divided genotype SNPs into two sets: (1) one set of top ranked disorder-associated SNPs within the selection threshold; and (2) the other set of the remaining genotype SNPs. GCTA was used to learn the genome-wide SNP heritability of a brain phenotype using a joint analysis of the two SNP set-based genetic components. The y-axis represents estimated SNP heritability contributable to the set of disorder-associated SNPs. Error bars represent the analytic standard errors of the estimates. Heritability estimates for seven disorders are displayed using solid navy-color bars, while the null expectations (i.e., estimates calculated based on the proportion of SNPs with respect to the genome-wide SNP heritability of the corresponding brain phenotype) are marked by dashed gray-line bars. Brain phenotypes with enriched disorder-set-based heritability at FDR q ≤ 0.1 are highlighted with asterisk (*** uncorrected p<0.001; ** p <0.01; * p<0.05).