Protein QTL (pQTL) Resources

Protein quantitative trait loci (pQTL) identify genetic variants that influence protein abundance measured by mass spectrometry-based proteomics. This resource provides pQTL summary statistics, fine-mapping results, TWAS/qTWAS pre-trained models, and colocalization analyses across brain tissue, cerebrospinal fluid (CSF), and AD-relevant cohorts.

Overview

pQTL mapping was performed using the FunGen-xQTL pipeline. Protein abundance measurements from tandem mass tag (TMT) mass spectrometry underwent normalization, batch correction, and covariate adjustment prior to tensorQTL-based association testing. Fine-mapping was performed using SuSiE-RSS yielding posterior inclusion probabilities (PIPs) and credible sets.

Available Datasets

Brain Tissue

Cerebrospinal Fluid (CSF)

Analyses Performed

Single-Context Fine-Mapping

Fine-mapping using SuSiE-RSS per protein, providing:

• Posterior inclusion probabilities (PIPs)
• 95% credible sets
• Standardized effect sizes

Multi-Gene Fine-Mapping

Multi-gene fine-mapping for pQTLs jointly models co-regulated proteins in a genomic window, resolving signals shared across proteins. Results available at syn69670592.

Trans-pQTL Fine-Mapping

Genome-wide trans-pQTL analyses identify distant protein regulatory relationships. Trans-pQTL fine-mapping results for ROSMAP DLPFC are provided at ROSMAP DLPFC.

TWAS / qTWAS Models

Pre-trained pQTL-based TWAS models for protein-level AD association analyses:

• TWAS weight models (syn69670600): ROSMAP DLPFC, MSBB, Knight ADRC brain
• qTWAS models (syn69670611): quantile regression pQTL models
• cTWAS inputs (syn70095142): formatted for causal TWAS

Colocalization

ColocBoost multi-context colocalization and pairwise SuSiE-COLOC analyses identify shared pQTL signals across cohorts (syn69670597). AD GWAS–pQTL colocalization results are at syn69865816 and syn69670630.

Data Access