ARIC PWAS models

Author

Sabrina Mi

Published

September 8, 2021

The ARIC model for MetaXcan is in Box: https://uchicago.box.com/s/3sf4y4gv6c7zam0l5fxicpcd3zji5wzc

ARIC PWAS

The Atherosclerosis Risk in Communities Study (ARIC) generated genotype and proteomic data from a total of 9,084 participants (7,213 European Americans and 1,871 African Americans). The relative conectrations of plasma proteins or protein complexes was measured from blood samples using an aptamer-based approach. Genotyping of blood samples was imputed to the TOPMed reference panel (GRCh38).

Nilan Chatterjee et al analyzed cis-genetic regulation of the plasma proteome, generating PWAS through TWAS/Fusion pipeline. They study involved 4,665 SOMAmers measuring 4,491 unique plasma proteins or protein complexes encoded by 4,445 autosomal genes.

For details on the paper: https://www.biorxiv.org/content/10.1101/2021.03.15.435533v1.full

Generating the model

We created a prediction model compatible with MetaXcan software from the weights generated by Nilan Chatterjee et al’s PWAS study. The steps are documented below:

  1. Create prediction weights file
  2. Calculate covariances

Validation

We validated the model by running SPrediXcan on height and coronary artery disease GWAS, then comparing the results to association found from Whole Blood mashr models.

  1. GIANT height
  2. CARDIoGRAM+C4D CAD