Jacqueline S Dron1,2, Robert A Hegele1,2,3. 1. Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University. 2. Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University. 3. Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Abstract
PURPOSE OF REVIEW: With improved next-generation sequencing technology, open-access genetic databases and increased awareness of complex trait genetics, we are entering a new era of risk assessment in which genetic-based risk scores (GRSs) will play a clinical role. We review the concepts underlying polygenic models of disease susceptibility and challenges in clinical implementation. RECENT FINDINGS: Polygenic risk scores are currently used in genetic research on dyslipidemias and cardiovascular disease (CVD). Although the underlying principles for constructing polygenic scores for lipids are established, the lack of consensus on which score to use is indicated by the large number - about 50 - that have been published. Recently, large-scale polygenic scores for CVD appear to afford superior risk prediction compared to small-scale scores. Despite the potential benefits of GRSs, certain biases towards ethnicity and sex need to be worked through. SUMMARY: We are on the verge of clinical application of GRSs to provide incremental information on dyslipidemia and CVD risk above and beyond traditional clinical variables. Additional work is required to develop a consensus of how such scores will be constructed and measured in a validated manner, as well as clinical indications for their use.
PURPOSE OF REVIEW: With improved next-generation sequencing technology, open-access genetic databases and increased awareness of complex trait genetics, we are entering a new era of risk assessment in which genetic-based risk scores (GRSs) will play a clinical role. We review the concepts underlying polygenic models of disease susceptibility and challenges in clinical implementation. RECENT FINDINGS: Polygenic risk scores are currently used in genetic research on dyslipidemias and cardiovascular disease (CVD). Although the underlying principles for constructing polygenic scores for lipids are established, the lack of consensus on which score to use is indicated by the large number - about 50 - that have been published. Recently, large-scale polygenic scores for CVD appear to afford superior risk prediction compared to small-scale scores. Despite the potential benefits of GRSs, certain biases towards ethnicity and sex need to be worked through. SUMMARY: We are on the verge of clinical application of GRSs to provide incremental information on dyslipidemia and CVD risk above and beyond traditional clinical variables. Additional work is required to develop a consensus of how such scores will be constructed and measured in a validated manner, as well as clinical indications for their use.
Authors: Jaroslav A Hubacek; Dana Dlouha; Vera Adamkova; Lucie Schwarzova; Vera Lanska; Richard Ceska; Martin Satny; Michal Vrablik Journal: Mol Diagn Ther Date: 2019-08 Impact factor: 4.074
Authors: Justin R Clark; Matthew Gemin; Amer Youssef; Santica M Marcovina; Annik Prat; Nabil G Seidah; Robert A Hegele; Michael B Boffa; Marlys L Koschinsky Journal: J Lipid Res Date: 2022-04-22 Impact factor: 6.676
Authors: Julieta Lazarte; Jacqueline S Dron; Adam D McIntyre; Allan C Skanes; Lorne J Gula; Anthony S Tang; Rafik Tadros; Zachary W Laksman; Robert A Hegele; Jason D Roberts Journal: CJC Open Date: 2021-02-06