Figure 3. Scatter plots of bidirectional MR analyses using several models to examine causal relationships between total surface area (TSA) and cognitive performance (CP)²⁹ (Fig. 3A & 3B), as well as global mean cortical thickness (MTH) and schizophrenia (freeze3, SCZ3)⁴⁰ (Fig. 3C & 3D).

A. Total SA on cognitive performance.

B. Cognitive performance on total SA.

C. Mean TH on schizophrenia.

D. Schizophrenia on mean TH.

(A) Forward MR results of TSA on CP. (B) Reverse MR results of CP on TSA. Based on Fig.3A and 3B, TSA and CP show a bidirectional causal relationship. (C): Forward MR results of MTH on SCZ3. (D): Reverse MR results of SCZ3 on MTH. Based on Fig. 3C and 3D, there is only a forward causal relationship between MTH and SCZ3. Note: The error bars represent 95% Confidence Intervals of beta coefficients. The five models applied are all denoted: Black: GSMR, red: fixed-effect IVW, green: weighted median, blue: MR Egger, pink: MR PRESSO. The first method served as our main analysis, while the rest of the methods were used for sensitivity analyses. Before using the instruments, we detected and removed outliers with the HEIDI test. SA: total cortical surface area, TH: global mean cortical thickness, CP: cognitive performance,²⁹ SCZ3: schizophrenia PGC GWAS freeze3.⁴⁰

Regarding the sample size of GWASs, ΤSA, MTH= 51,665; CP=257,828; SCZ3=161,405.