The Spanish Polygenic Score reference distribution: a resource for personalized medicine

Area of Science:

• Genetics
• Population Genomics
• Bioinformatics

Background:

• Polygenic Scores (PGS) are crucial for understanding genetic contributions to complex diseases and traits.
• Population-specific genetic architecture influences disease risk and necessitates tailored analyses.
• Previous studies have lacked comprehensive PGS distributions for diverse diseases within the Spanish population.

Purpose of the Study:

• To establish comprehensive Polygenic Score (PGS) distributions for 3124 common diseases and quantitative traits in a Spanish cohort.
• To investigate the genetic architecture of diseases and traits within the Spanish population.
• To provide a reproducible data processing pipeline and a web interface for accessing PGS reference distributions.

Main Methods:

• Genome and exome data from 2190 unrelated individuals of Spanish ancestry were analyzed.
• Polygenic Scores were computed for 3124 common diseases and quantitative traits.
• Pairwise correlations between disease and trait PGS were explored.

Main Results:

• Established PGS distributions for a wide array of diseases (e.g., cancer, digestive, cardiovascular, neuronal, immune) and quantitative traits (e.g., hematological, anthropometric) in the Spanish population.
• Identified significant pairwise correlations between various disease and trait PGS, suggesting shared genetic underpinnings.
• Developed and shared a data processing pipeline for PGS computation and a web interface (SpPGS Atlas) for exploring reference distributions.

Conclusions:

• The generated PGS distributions offer valuable insights into the genetic basis of traits and diseases in the Spanish population.
• Findings support personalized medicine approaches and public health interventions tailored to this population.
• The provided resources enhance reproducibility and accessibility of PGS data for global research.