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

Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases . 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-... Full description

Journal Title: Nature medicine 2020-04, Vol.26 (4), p.549-557
Main Author: Mars, Nina
Other Authors: Koskela, Jukka T , Ripatti, Pietari , Kiiskinen, Tuomo T J , Havulinna, Aki S , Lindbohm, Joni V , Ahola-Olli, Ari , Kurki, Mitja , Karjalainen, Juha , Palta, Priit , Neale, Benjamin M , Daly, Mark , Salomaa, Veikko , Palotie, Aarno , Widén, Elisabeth , Ripatti, Samuli
Format: Electronic Article Electronic Article
Language: English
Subjects:
Age
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/32273609
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title: Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers
format: Article
creator:
  • Mars, Nina
  • Koskela, Jukka T
  • Ripatti, Pietari
  • Kiiskinen, Tuomo T J
  • Havulinna, Aki S
  • Lindbohm, Joni V
  • Ahola-Olli, Ari
  • Kurki, Mitja
  • Karjalainen, Juha
  • Palta, Priit
  • Neale, Benjamin M
  • Daly, Mark
  • Salomaa, Veikko
  • Palotie, Aarno
  • Widén, Elisabeth
  • Ripatti, Samuli
subjects:
  • Added value
  • Adult
  • Age
  • Age of Onset
  • Analysis
  • Biomarkers - analysis
  • Breast cancer
  • Breast Neoplasms - diagnosis
  • Breast Neoplasms - epidemiology
  • Breast Neoplasms - genetics
  • Cancer
  • Cardiac arrhythmia
  • Cardiovascular disease
  • Cardiovascular diseases
  • Cardiovascular Diseases - diagnosis
  • Cardiovascular Diseases - epidemiology
  • Cardiovascular Diseases - genetics
  • Case-Control Studies
  • Coronary artery disease
  • Demographic aspects
  • Diabetes
  • Diabetes mellitus
  • Diabetes mellitus (non-insulin dependent)
  • Diabetes Mellitus, Type 2 - diagnosis
  • Diabetes Mellitus, Type 2 - epidemiology
  • Diabetes Mellitus, Type 2 - genetics
  • Female
  • Fibrillation
  • Finland - epidemiology
  • Genetic aspects
  • Genetic Markers - genetics
  • Genetic Predisposition to Disease - epidemiology
  • Genetic susceptibility
  • Genome-Wide Association Study
  • Genomes
  • Health aspects
  • Health risk assessment
  • Health risks
  • Heart diseases
  • Humans
  • Male
  • Metabolic diseases
  • Metabolic Diseases - diagnosis
  • Metabolic Diseases - epidemiology
  • Metabolic Diseases - genetics
  • Middle Aged
  • Multifactorial Inheritance
  • Multifactorial traits
  • Neoplasms - diagnosis
  • Neoplasms - epidemiology
  • Neoplasms - genetics
  • Polymorphism, Single Nucleotide
  • Predictions
  • Predictive Value of Tests
  • Prognosis
  • Prostate cancer
  • Prostatic Neoplasms - diagnosis
  • Prostatic Neoplasms - epidemiology
  • Prostatic Neoplasms - genetics
  • Reclassification
  • Risk analysis
  • Risk Assessment
  • Risk Factors
  • Service life assessment
  • Young Adult
ispartof: Nature medicine, 2020-04, Vol.26 (4), p.549-557
description: Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases . 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titlePolygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers
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descriptionPolygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases . 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.
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subjectAdded value ; Adult ; Age ; Age of Onset ; Analysis ; Biomarkers - analysis ; Breast cancer ; Breast Neoplasms - diagnosis ; Breast Neoplasms - epidemiology ; Breast Neoplasms - genetics ; Cancer ; Cardiac arrhythmia ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - diagnosis ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Case-Control Studies ; Coronary artery disease ; Demographic aspects ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - genetics ; Female ; Fibrillation ; Finland - epidemiology ; Genetic aspects ; Genetic Markers - genetics ; Genetic Predisposition to Disease - epidemiology ; Genetic susceptibility ; Genome-Wide Association Study ; Genomes ; Health aspects ; Health risk assessment ; Health risks ; Heart diseases ; Humans ; Male ; Metabolic diseases ; Metabolic Diseases - diagnosis ; Metabolic Diseases - epidemiology ; Metabolic Diseases - genetics ; Middle Aged ; Multifactorial Inheritance ; Multifactorial traits ; Neoplasms - diagnosis ; Neoplasms - epidemiology ; Neoplasms - genetics ; Polymorphism, Single Nucleotide ; Predictions ; Predictive Value of Tests ; Prognosis ; Prostate cancer ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - epidemiology ; Prostatic Neoplasms - genetics ; Reclassification ; Risk analysis ; Risk Assessment ; Risk Factors ; Service life assessment ; Young Adult
ispartofNature medicine, 2020-04, Vol.26 (4), p.549-557
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descriptionPolygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases . 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.
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6Breast cancer
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9Breast Neoplasms - genetics
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11Cardiac arrhythmia
12Cardiovascular disease
13Cardiovascular diseases
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17Case-Control Studies
18Coronary artery disease
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22Diabetes mellitus (non-insulin dependent)
23Diabetes Mellitus, Type 2 - diagnosis
24Diabetes Mellitus, Type 2 - epidemiology
25Diabetes Mellitus, Type 2 - genetics
26Female
27Fibrillation
28Finland - epidemiology
29Genetic aspects
30Genetic Markers - genetics
31Genetic Predisposition to Disease - epidemiology
32Genetic susceptibility
33Genome-Wide Association Study
34Genomes
35Health aspects
36Health risk assessment
37Health risks
38Heart diseases
39Humans
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41Metabolic diseases
42Metabolic Diseases - diagnosis
43Metabolic Diseases - epidemiology
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46Multifactorial Inheritance
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49Neoplasms - epidemiology
50Neoplasms - genetics
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titlePolygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers
authorMars, Nina ; Koskela, Jukka T ; Ripatti, Pietari ; Kiiskinen, Tuomo T J ; Havulinna, Aki S ; Lindbohm, Joni V ; Ahola-Olli, Ari ; Kurki, Mitja ; Karjalainen, Juha ; Palta, Priit ; Neale, Benjamin M ; Daly, Mark ; Salomaa, Veikko ; Palotie, Aarno ; Widén, Elisabeth ; Ripatti, Samuli
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57Prostatic Neoplasms - epidemiology
58Prostatic Neoplasms - genetics
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60Risk analysis
61Risk Assessment
62Risk Factors
63Service life assessment
64Young Adult
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abstractPolygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases . 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.
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