Polygenic scores in biomedical research

Nat Rev Genet. 2022 Sep;23(9):524-532. doi: 10.1038/s41576-022-00470-z.

Iftikhar J Kullo ¹, Cathryn M Lewis ², Michael Inouye ³ ⁴, Alicia R Martin ⁵ ⁶, Samuli Ripatti ⁷ ⁸ ⁹ ¹⁰, Nilanjan Chatterjee ¹¹

Affiliations

1 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. [email protected].
2 Social, Genetic and Developmental Psychiatry Centre & Department of Medical & Molecular, King's College London, London, UK. [email protected].
3 Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [email protected].
4 Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. [email protected].
5 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. [email protected].
6 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. [email protected].
7 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. [email protected].
8 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. [email protected].
9 Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. [email protected].
10 Department of Public Health, University of Helsinki, Helsinki, Finland. [email protected].
11 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [email protected].

PMID: 35354965 DOI: 10.1038/s41576-022-00470-z

Abstract

Public health strategies aimed at disease prevention or early detection and intervention have the potential to advance human health worldwide. However, their success depends on the identification of risk factors that underlie disease burden in the general population. Genome-wide association studies (GWAS) have implicated thousands of single-nucleotide polymorphisms (SNPs) in common complex diseases or traits. By calculating a weighted sum of the number of trait-associated alleles harboured by an individual, a polygenic score (PGS), also called a polygenic risk score (PRS), can be constructed that reflects an individual’s estimated genetic predisposition for a given phenotype. Here, we ask six experts to give their opinions on the utility of these probabilistic tools, their strengths and limitations, and the remaining barriers that need to be overcome for their equitable use.

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