PRSice

PRSice calculates polygenic risk scores (PRS) across P-value thresholds to evaluate genetic liability for complex traits and enable PRS-based association and prediction analyses.

Key Features:

• High-Resolution Calculation: Calculates PRS at numerous P-value thresholds to identify best-fit PRS configurations.
• Threshold Flexibility: Generates results across a configurable range of P-value thresholds to support broad and specific analyses.
• Linkage Disequilibrium Thinning: Performs Single Nucleotide Polymorphism (SNP) thinning based on linkage disequilibrium and P-values or can include all SNPs.
• Data Compatibility: Handles both genotyped and imputed genetic data.
• Ancestry-Informative Variables: Incorporates ancestry-informative covariates into PRS analyses.
• Multi-Trait Application: Applies PRS across multiple traits within a single run.
• Implementation and Dependencies: Implemented in R with bash data-management scripts and uses PLINK-1.9 for genotype processing and score calculation.

Scientific Applications:

• Detection of Shared Genetic Aetiology: Analyzes PRS across traits to detect shared genetic factors contributing to multiple conditions.
• Genetic Signal Identification: Aggregates effect sizes across loci to improve detection of genetic signal in underpowered studies.
• Trait Architecture Inference: Evaluates PRS performance across thresholds to infer aspects of the genetic architecture of complex traits.
• Clinical Trial Screening and Biomarker Development: Uses PRS as phenotype-associated biomarkers to stratify individuals for clinical trial screening.

Methodology:

Calculates PRS at multiple P-value thresholds, identifies the best-fit PRS and estimates P-value significance thresholds, performs LD-based SNP thinning or uses all SNPs, handles genotyped and imputed data, incorporates ancestry-informative variables, applies PRS across multiple traits, and is implemented in R with bash scripts and PLINK-1.9; it has been applied to schizophrenia, major depressive disorder, and smoking datasets.