Table 2 Comparisons of the component of the common neurobiological substrate (CCS) and the CCS genetic architecture with psychiatric disorders.

LD score regression (LDSC)
GWAS comparison	r_g	p value
Psychiatric cross-disorder	0.0005	0.99
Bipolar disorder	0.17	0.08
Major depression	−0.03	0.75
Schizophrenia	0.08	0.38
Rank–rank hypergeometric overlap (RRHO)
GWAS comparison	Overlap	p value
Psychiatric cross-disorder	0.29	0.53
Bipolar disorder	0.21	0.06
Major depression	0.04	0.18
Schizophrenia	0.02	0.15
Binomial sign tests (p < 0.05)
GWAS comparison	Probability	p value
Psychiatric cross-disorder	0.50	0.77
Bipolar disorder	0.50	0.67
Major depression	0.50	0.82
Schizophrenia	0.50	0.64
Binomial sign tests (p < 1 × 10⁻⁵)
GWAS comparison	Probability	p value
Psychiatric cross-disorder	0.33	0.93
Bipolar disorder	0.54	0.50
Major depression	0.33	0.93
Schizophrenia	0.54	0.50
Polygenic scores (PGS)
Training GWAS	Effect size	p value	p_T
Psychiatric cross-disorder	−0.78	0.30	5 × 10⁻⁸
Bipolar disorder	−0.64	0.05	1 × 10⁻⁷
Major depression	−5.01	0.31	1 × 10⁻²
Schizophrenia	−0.58	0.24	1 × 10⁻⁷

Details on the four training genome-wide association studies (GWAS) datasets are provided in the Methods section. LDSC: linkage disequilibrium score regression using genome-wide summary statistics (Supplementary Table S10); r_g genetic correlation. RRHO: rank–rank hypergeometric overlap test showing the relative overlap of genome-wide summary statistics (Supplementary Table S11). Sign tests one-sided binomial sign tests for CCS GWAS p value thresholds p < 0.05 and p < 1 × 10⁻⁵ and the corresponding probability of success (Supplementary Table S12). PGS association of polygenic scores with the CCS; pT training GWAS data p value threshold; effect size linear regression effect size at the pT showing the strongest support for an association (see Supplementary Table S13 for results of all ten thresholds); p value: one-sided p value not corrected for multiple testing. The significance level adjusted for multiple testing was α = 0.05/(10 × 4) = 0.00125.

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