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. Author manuscript; available in PMC: 2019 Sep 1.
Published in final edited form as: Nat Neurosci. 2019 Jan 28;22(3):353–361. doi: 10.1038/s41593-018-0320-0

Figure 4.

Figure 4.

LDSC-SEG heritability partitioning. (A) −log10 one-sided p-values from LDSC-SEG enrichment tests for the iPSYCH XDX GWAS (n=46,008 cases, 19,526 controls) highlight significant (two-tailed p < 8.32×10−5, Bonferroni correction for 601 LDSC-SEG enrichment tests) and/or suggestive (FDR < 0.05) enrichment for heritability in SNP sets related to gene regulation in fetal brain tissue. Exact p-values and effect sizes in Supplementary Table 17. (B) −log10 one-sided LDSC-SEG enrichment test p-values for the same fetal brain SNP sets in the eSCZ (n=34,241 cases, 45,604 controls) and eXDX (n=33,332 cases, 27,888 controls) GWAS replicate enrichments (two-tailed p < 0.002, Bonferroni correction for 24 replication enrichment tests). Exact p-values and effect sizes in Supplementary Table 19. (C) The magnitude of LDSC-SEG enrichment effect estimates for fetal brain tissues in the XDX GWAS (orange) are not qualitatively different when excluding single case groups (non-orange). Grey shading denotes bunches of estimate replicates. Bars denote 95% confidence intervals. Exact effect sizes and sample sizes in Supplementary Table 20. CNS, central nervous system; Axis numbers (A,B,C) denote SNPs sets defined by narrow peaks of 1, DNase, DNase I Hypersensitivity; 2, H3K27ac, Histone H3, Lysine 27 acetylation; 3, H3K36me3, Histone H3, Lysine 36 tri-methylation; 4, H3K4me, Histone H3, Lysine 4 methylation; 5, H3K4me3, Histone H3, Lysine 4 tri-methylation; 6, H3K9ac, Histone H3, Lysine 9 acetylation. AG, Adult Angular Gyrus; AC, Adult Anterior Caudate; CG, Adult Cingulate Gyrus; dlPFC, Adult Dorsolateral Prefrontal Cortex; Hipp, Adult Hippocampus; ITL, Adult Inferior Temporal Lobe; SN, Adult Substantia Nigra; cCortex, Cortex Derived Cultured Neurospheres; cGE, Ganglion Eminence Derived Cultured Neurospheres; GM, Gemrinal Matrix; fFetal, female Fetal Brain; mFetal, male Fetal Brain; eXDX, external cross-disorder GWAS; eSCZ, external schizophrenia GWAS; ADHD, attention-deficit, hyperactivity disorder; AFF, affective disorder; ANO, anorexia; ASD, autism-spectrum disorder; BIP, bipolar disorder; SCZ, schizophrenia; OTH, other indications not falling within individual disorder categories.