Genomic atlas of the human proteome from brain, CSF and plasma: Improvement with TOPMed imputed genomics

Abstract

Comprehensive expression quantitative trait loci (eQTL) studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated GWAS loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein QTL (pQTL) in neurologically relevant tissues. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high-quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in CSF, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 pQTL in brain, 30 pQTL in CSF, and 22 pQTL in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These pQTL findings are assessable through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer (ONTIME) for use by the scientific community.