Abstract
The impact of genetic variants on gene expression has been intensely studied at the transcription level and the results have been useful in linking genes to disease risk for complex disorders, such as schizophrenia. On the other hand, the downstream impact of these variants and the molecular mechanisms connecting transcription variation to disease risk are not well understood. To this end, we quantitated ribosome occupancy in prefrontal cortex samples of the BrainGVEx cohort. Together with RNA-Seq and proteomics data from the same cohort, we performed cis-Quantitative Trait Locus (QTL) mapping to identify variants associated with transcription (eQTL), ribosome occupancy (rQTL), and protein (pQTL) level. We found that while more than half of pQTL effects originated from transcription variation, less than half of the eQTL effects propagated to the protein level. Leveraging multi-omics QTL results, we found 50 schizophrenia risk genes and further identified driver mechanisms for ten. We also found risk genes that have clear eQTL signals without discernible pQTLs.
Summary Attenuation of eQTL effects at the protein level was found prevalent in the human brain and its relevance in schizophrenia risk was investigated.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
‡ PsychENCODE Consortium authors and affiliations are listed in the supplementary materials.
