The pQTL summary statistics are available in the “Open Access Dataset” tab.
To access the proteomic data, please log into DSS and submit an application.
Within the application, add this dataset (accession NG00102) in the “Choose a Dataset” section.
Once approved, you will be able to log in and access the data within the DARM portal.

Description

Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. We previously 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 now enhanced 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. 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 is part of the Knight ADRC Collection. Other datasets in this collection can be found at: https://www.niagads.org/knight-adrc-collection

Sample Summary per Data Type

Available Filesets

NameAccessionLatest ReleaseDescription
KGAD Proteomics: pQTL summary statistics and protein annotations (open access)fsa000065NG00102.v1pQTL summary statistics and protein annotations
KGAD Proteomics: Proteomics, protein annotations, and QC documents (application needed)fsa000066NG00102.v1Proteomics, protein annotations, and QC documents

View the File Manifest for a full list of files released in this dataset.

Provided in this dataset is a set of multi-tissue proteomic data that underwent a process of quality control measures by the Cruchaga Lab at Washington University in St. Louis, as well as pQTL summary statistics. From 1157 subjects, 1300 protein analytes were measured for 328 brain samples, 869 protein analytes were measured for 770 CSF samples, and 953 protein analytes were measured for 500 plasma samples on the SomaLogic SomaScan 1.3K platform at the Washington University Neurogenomics and Informatics Center.

Consent LevelNumber of Subjects
DS-ADRD-IRB-PUB1151
HMB-IRB-PUB6

Visit the Data Use Limitations page for definitions of the consent levels above.