PRS

PRS aggregates polygenic risk scores from genome-wide association studies (GWAS) to quantify genetic liability and investigate associations with human phenotypes for studies of complex disease etiology.

Key Features:

• Extensive Data Integration: Incorporates 162 polygenic risk scores identified through GWAS with a significance threshold of P < 5×10^-5 and analyzed across 551 heritable traits measured in UK Biobank (n = 334,398).
• Phenome-wide Evaluation: Enables phenome-wide analyses exemplified by assessment of schizophrenia PRS that revealed inverse associations with cognitive function measures.
• Mendelian Randomization Evidence: Associations identified in phenome-wide screens have been further evaluated using Mendelian randomization (MR) analyses indicating potential causal relationships.
• Advanced Analytical Frameworks: Supports mediation analysis and multivariable MR frameworks to dissect the effects of multiple risk factors on disease outcomes.

Scientific Applications:

• Marker Discovery: Identification of novel genetic markers linked to disease susceptibility across a broad set of phenotypes.
• Causal Pathway Analysis: Exploration of causal relationships between genetic liability and phenotypic traits using MR and related frameworks.
• Risk Factor Decomposition: Assessment of the interplay and mediating effects of multiple genetic and environmental risk factors in disease etiology.

Methodology:

PRS were selected from GWAS at P < 5×10^-5 and analyzed across UK Biobank phenotypes using phenome-wide evaluation, Mendelian randomization (MR) analyses, mediation analysis, and multivariable MR frameworks.