Polygenic risk scores: from research tools to clinical instruments
Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individ...
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| Published in: | Genome medicine Vol. 12; no. 1; p. 44 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
BioMed Central Ltd
18-05-2020
BioMed Central BMC |
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| Online Access: | Get full text |
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| Abstract | Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual's susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual's lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual's PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation. |
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| AbstractList | Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual's susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual's lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual's PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation. Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual's susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual's lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual's PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation. Keywords: Genetics, Common disorders, Polygenic risk scores, Prediction, Pharmacogenetics, Risk Abstract Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual’s susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual’s PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation. |
| ArticleNumber | 44 |
| Audience | Academic |
| Author | Lewis, Cathryn M Vassos, Evangelos |
| Author_xml | – sequence: 1 givenname: Cathryn M orcidid: 0000-0002-8249-8476 surname: Lewis fullname: Lewis, Cathryn M email: cathryn.lewis@kcl.ac.uk, cathryn.lewis@kcl.ac.uk organization: Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, UK. cathryn.lewis@kcl.ac.uk – sequence: 2 givenname: Evangelos surname: Vassos fullname: Vassos, Evangelos organization: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, de Crespigny Park, London, SE5 8AF, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32423490$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Biotechnology industries Common disorders Direct-To-Consumer Screening and Testing Disease susceptibility Genealogy Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic Variation Genetics Genome-wide association studies Genomes Genomics Humans Initiatives Minority & ethnic groups Multifactorial Inheritance Pharmacogenetics Polygenic risk scores Population Prediction Research Design Review Risk Risk assessment Risk Factors Studies Type 2 diabetes |
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| Title | Polygenic risk scores: from research tools to clinical instruments |
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