Our findings should be interpreted in the context of its limitations. First, we are likely limited by the number of reference brain proteomes since about 18% (1468 / 8356) of the cis-regulated protein abundances could be estimated using 376 reference proteomes whereas 49% (6,735 /13,650) of the cis-regulated brain transcripts could be estimated from 888 reference transcriptomes. Nevertheless, we found 7 genes by TWAS and 1 gene by PWAS that were consistent with prior work using independent and smaller TWAS datasets26 (Supplementary Table 19). Second, we were limited by the stochastic nature of the discovery-based approach used to generate the human brain proteomes, which limited our ability to replicate 6 of the 19 proteins identified in the discovery PWAS. Both issues can be alleviated by larger brain proteomic datasets to estimate the genetic effect on protein abundance for more brain proteins. Despite these limitations, we presented results from the largest and deepest set of human brain proteomes available to our knowledge.
