comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores

Area of Science:

• Genetics
• Bioinformatics
• Computational Biology

Background:

• Polygenic scores (PGS) assess genetic liability for complex traits, but their use in identifying shared genetic predispositions between phenotypes is limited.
• Understanding shared genetic factors between conditions like blood pressure and cancer is crucial for comprehensive risk assessment.

Purpose of the Study:

• To develop and introduce the comorbidPGS R package for systematically evaluating shared genetic effects between correlated phenotypes using PGS.
• To investigate the shared genetic predisposition between blood pressure traits and various cancers.

Main Methods:

• Developed the comorbidPGS R package that utilizes single nucleotide polymorphisms (SNPs) and their effect sizes on a primary phenotype (Po-PGS).
• Applied the package to analyze shared genetic risks between blood pressure phenotypes (SBP, DBP, pulse pressure) and cancers (breast, pancreatic, kidney, prostate, colorectal).
• Utilized UK Biobank data and independent GWAS summary statistics from European ancestry individuals.

Main Results:

• Identified a significant association between elevated diastolic blood pressure (DBP) and the genetic risk of prostate cancer (PrC).
• Found significant associations between colorectal cancer (CrC) PGS and lower systolic blood pressure (SBP) and DBP.
• Observed nominally significant associations between genetic predisposition to elevated SBP and increased risk of kidney cancer (KidC) and PrC.

Conclusions:

• The comorbidPGS package effectively highlights mechanistic relationships between blood pressure regulation and susceptibility to specific malignancies.
• The findings underscore shared genetic underpinnings between cardiovascular traits and cancer development, offering new avenues for research.
• ComorbidPGS provides a valuable tool for exploring shared genetic susceptibility across diverse and related phenotypes.