SMR and HEIDI on the PWAS significant genes to remove genes with SMR p ≥ 0.05, HEIDI p ≤ 0.05, or in cases where HEIDI p was unable to be determined. The goal of these additional tests is to focus on genes with evidence that their genetically regulated protein abundance mediates their association with the trait of interest and to remove genes likely to be the result of linkage disequilibrium. After considering findings from FUSION, SMR, and HEIDI, we identified 46 genes in neuroticism, 216 genes in BMI, and 117 genes in WHRadjBMI that likely contribute to these traits by modulating their brain protein abundance (Supplementary Tables 10–12). As expected, 11 of 46 (24%) of the neuroticism genes were also identified by the depression PWAS, which reflects their high degree of genetic correlation. By contrast, 4 of 216 (2%) of the BMI genes and 4 of 117 (3%) of the WHRadjBMI genes overlapped with the 19 depression PWAS-significant genes.
