Polygenic risk scores in psychiatry: Will they be useful for clinicians?
paper
Cited
Public
- Authors
- Fullerton, Janice M; Nurnberger, John I
- Year
- 2019
- Journal
- F1000Research
- PMID
- 31448085
- DOI
- 10.12688/f1000research.18491.1
- PMCID
- PMC6676506
Major psychiatric disorders are heritable but they are genetically complex. This means that, with certain exceptions, single gene markers will not be helpful for diagnosis. However, we are learning more about the large number of gene variants that, in combination, are associated with risk for disorders such as schizophrenia, bipolar disorder, and other psychiatric conditions. The presence of those risk variants may now be combined into a polygenic risk score (PRS). Such a score provides a quantitative index of the genomic burden of risk variants in an individual, which relates to the likelihood that a person has a particular disorder. Currently, such scores are quite useful in research, and they are telling us much about the relationships between different disorders and other indices of brain function. In the future, as the datasets supporting the development of such scores become larger and more diverse and as methodological developments improve predictive capacity, we expect that PRS will have substantial clinical utility in the assessment of risk for disease, subtypes of disease, and even treatment response. Here, we provide an overview of PRS in general terms (including a glossary suitable for informed non-geneticists) and discuss the use of PRS in psychiatry, including their limitations and cautions for interpretation, as well as their applications now and in the future.
An example of the population distributions of polygenic risk scores (PRS).The black lines represent the distribution of PRS for a complex genetic condition in the (top) general population and (bottom) a case population of individuals affected with the condition. At a population level, the average PRS in the case group is higher than the average PRS in the control group, although many cases will have lower scores than the average person from the general population. The red line indicates a single individual with a “high PRS” – this individual has a score which lies in the top 94% in the general population and the top 90% in case population.
Potential clinical uses of polygenic risk scores.BP, bipolar disorder; BP1, bipolar disorder - type 1, BP2, bipolar disorder - type 2, ECT, electroconvulsive therapy; MDD, major depressive disorder; SA, schizoaffective disorder; SZ, schizophrenia.
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In this knowledge base
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| High Polygenic Risk Scores Are Associated With Early Age of Onset of Alcohol Use Disorder in Adolescents and Young Adults at Risk. | 2022 | 36324664 |
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