Abstract
Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated 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 quantitative trait loci in brain, cerebrospinal fluid, and plasma. 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 cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.