We’re moving! Datasets in the NIAGADS database are being transitioned to the DSS database, more info coming soon.
Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer’s disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer’s disease, Parkinson’s disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases.
This dataset includes Individual-level data (proteomics + array-based genotype data after imputation), consent information, and summary statistics, below are the README files
Individual-level data README
Summary statistics README
Individual-level data (size - 5GB) is accessible through formal data request.
Summary statistics (pQTL) data is freely available. The data exceeds 500Gb, so please email email@example.com to set up an FTP transfer of the data.
This dataset is part of the Knight ADRC Collection. Other datasets in this collection can be found at: https://www.niagads.org/knight-adrc-collection
The summary statistics for all the analyses can be easily explored in the ONTIME (Online Neurodegenerative Trait Integrative Multi-Omics Explorer) pheweb (https://ontime.wustl.edu/).
Peer-reviewed publication available via: https://www.nature.com/articles/s41593-021-00886-6
This work was supported by grants from the National Institutes of Health (R01AG044546, P01AG003991, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501 and R01AG057777), the Alzheimer Association (NIRG-11-200110, BAND-14-338165, AARG-16-441560 and BFG-15-362540). This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, and the Departments of Neurology and Psychiatry at Washington University School of Medicine. The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681, P01 AG03991, and P01 AG026276.