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comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores.
Pascat, Vincent; Zudina, Liudmila; Ulrich, Anna; Maina, Jared G; Kaakinen, Marika; Pupko, Igor; Bonnefond, Amélie; Demirkan, Ayse; Balkhiyarova, Zhanna; Froguel, Philippe; Prokopenko, Inga.
Afiliación
  • Pascat V; INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France.
  • Zudina L; University of Lille, Lille University Hospital, Lille, France.
  • Ulrich A; Imperial College London, Section of Genomics of Systems Medicine, Department of Metabolism, London, UK.
  • Maina JG; Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
  • Kaakinen M; Imperial College London, Section of Genomics of Systems Medicine, Department of Metabolism, London, UK.
  • Pupko I; Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
  • Bonnefond A; Imperial College London, Section of Genomics of Systems Medicine, Department of Metabolism, London, UK.
  • Demirkan A; Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
  • Balkhiyarova Z; INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France.
  • Froguel P; University of Lille, Lille University Hospital, Lille, France.
  • Prokopenko I; Imperial College London, Section of Genomics of Systems Medicine, Department of Metabolism, London, UK.
Hum Hered ; 89(1): 60-70, 2024.
Article en En | MEDLINE | ID: mdl-38740014
ABSTRACT

INTRODUCTION:

Polygenic score (PGS) is a valuable method for assessing the estimated genetic liability to a given outcome or genetic variability contributing to a quantitative trait. While polygenic risk scores are widely used for complex traits, their application in uncovering shared genetic predisposition between phenotypes, i.e., when genetic variants influence more than one phenotype, remains limited.

METHODS:

We developed an R package, comorbidPGS, which facilitates a systematic evaluation of shared genetic effects among (cor)related phenotypes using PGSs. The comorbidPGS package takes as input a set of single nucleotide polymorphisms along with their established effects on the original phenotype (Po), referred to as Po-PGS. It generates a comprehensive summary of effect(s) of Po-PGS on target phenotype(s) (Pt) with customisable graphical features.

RESULTS:

We applied comorbidPGS to investigate the shared genetic predisposition between phenotypes defining elevated blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP; pulse pressure) and several cancers (breast cancer; pancreatic cancer, PanC; kidney cancer, KidC; prostate cancer, PrC; colorectal cancer, CrC) using the European ancestry UK Biobank individuals and GWAS meta-analyses summary statistics from independent set of European ancestry individuals. We report a significant association between elevated DBP and the genetic risk of PrC (ß [SE] = 0.066 [0.017], p value = 9.64 × 10-5), as well as between CrC PGS and both, lower SBP (ß [SE] = -0.10 [0.029], p value = 3.83 × 10-4) and lower DBP (ß [SE] = -0.055 [0.017], p value = 1.05 × 10-3). Our analysis highlights two nominally significant relationships for individuals with genetic predisposition to elevated SBP leading to higher risk of KidC (OR [95% CI] = 1.04 [1.0039-1.087], p value = 2.82 × 10-2) and PrC (OR [95% CI] = 1.02 [1.003-1.041], p value = 2.22 × 10-2).

CONCLUSION:

Using comorbidPGS, we underscore mechanistic relationships between blood pressure regulation and susceptibility to three comorbid malignancies. This package offers valuable means to evaluate shared genetic susceptibility between (cor)related phenotypes through polygenic scores.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Predisposición Genética a la Enfermedad / Herencia Multifactorial / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Límite: Female / Humans / Male Idioma: En Revista: Hum Hered Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Predisposición Genética a la Enfermedad / Herencia Multifactorial / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Límite: Female / Humans / Male Idioma: En Revista: Hum Hered Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza