Figure 1.

Genetic pleiotropy enrichment of schizophrenia (SCZ) conditional on MS. (a) Conditional Q-Q plot of nominal versus empirical −log₁₀ P-values (corrected for inflation) in SCZ below the standard GWAS threshold of P<5 × 10⁻⁸ as a function of significance of association with multiple sclerosis (MS) at the level of −log₁₀(P)⩾0, −log₁₀(P)⩾1, −log₁₀(P)⩾2, −log₁₀(P)⩾3 corresponding to P⩽1, P⩽0.1, P⩽0.01, P⩽0.001, respectively. Dotted lines indicate the null hypothesis. (b) Conditional true discovery rate (TDR) plots illustrating the increase in TDR associated with increased pleiotropic enrichment in SCZ conditioned on MS (SCZ|MS). (c) Cumulative replication plot showing the average rate of replication (P<0.05) within SCZ substudies for a given P-value threshold shows that pleiotropic enriched SNP categories replicate at a higher rate in independent SCZ samples, for SCZ conditioned on MS (SCZ|MS). The vertical intercept is the overall replication rate per category. (d) Z-score-z-score plot demonstrates that the empirical replication z-scores closely match the expected a posteriori effect sizes of SCZ and are strongly dependent upon pleiotropy with MS. Analysis is based on split half method of the 17 PGC SCZ substudies.