HOPS

HOPS quantifies horizontal pleiotropy by calculating the Horizontal Pleiotropy Score from genome-wide association summary statistics to identify genetic variants that independently influence multiple phenotypic traits.

Key Features:

• Horizontal Pleiotropy Quantification: Calculates the Horizontal Pleiotropy Score (HOPS) from genome-wide association summary statistics to quantify instances where single variants affect multiple traits independently.
• Large-scale GWAS Application: Applied to summary statistics for 372 heritable phenotypes derived from 361,194 individuals in the UK Biobank.
• Pleiotropy Characterization: Identifies pervasive horizontal pleiotropy across the genome and highlights its prominence among highly polygenic phenotypes and active regulatory regions.

Scientific Applications:

• Genetic architecture analysis: Dissects the contribution of horizontally pleiotropic variants to the genetic architecture of complex traits and diseases.
• Polygenicity and regulatory enrichment: Assesses the prevalence of horizontal pleiotropy among highly polygenic phenotypes and within active regulatory regions.
• Variant interpretation in GWAS: Provides a metric to interpret how individual variants may contribute to multiple phenotypic outcomes using GWAS summary statistics.

Methodology:

Computes the Horizontal Pleiotropy Score from genome-wide association summary statistics to detect variants that independently affect multiple traits, applied to UK Biobank summary statistics for 372 phenotypes from 361,194 individuals.