From Basic Science to Clinical Application of Polygenic Risk Scores

作者：Naomi R. Wray, Tian Lin, Jehannine Austin, John J. McGrath, Ian B. Hickie, Graham K. Murray, Peter M. Visscher · 发表于：JAMA Psychiatry · 年份：2020 · DOI：10.1001/jamapsychiatry.2020.3049 · 被引用次数：405 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Folate and B Vitamins Research

Importance: Polygenic risk scores (PRS) are predictors of the genetic susceptibilities of individuals to diseases. All individuals have DNA risk variants for all common diseases, but genetic susceptibility differences between people reflect the cumulative burden of these. Polygenic risk scores for an individual are calculated as weighted counts of thousands of risk variants that they carry, where the risk variants and their weights have been identified in genome-wide association studies. Here, we review the underlying basic science of PRS, providing a foundation for understanding the potential clinical utility and limitations of PRS. Observations: Polygenic risk scores can be calculated for a wide range of diseases from a saliva or blood sample using genotyping technologies that are inexpensive. While genotyping only needs to be done once for each individual in their lifetime, the PRS can be recalculated as identification of risk variants improves. On their own, PRS will never be able to establish or definitively predict future diagnoses of common complex conditions because genetic factors only contribute part of the risk, and PRS will only ever capture part of the genetic contributions. Nonetheless, just as clinical medicine uses a multitude of other predictive measures, PRS either on their own or as part of multivariable predictive algorithms could play a role. Conclusions and Relevance: Utility of PRS in clinical medicine and ethical issues related to their use should be e...