Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases1,2,3. We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies.
Original languageEnglish
JournalNature Medicine
Volume2020
Issue number26
Pages (from-to)549-557
Number of pages9
ISSN1078-8956
DOIs
Publication statusPublished - 7 Apr 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1184 Genetics, developmental biology, physiology
  • 3111 Biomedicine

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