scholarly journals A polygenic risk score for coronary heart disease performs well in individuals aged 70 years and older

2021 ◽  
Author(s):  
Johannes T Neumann ◽  
Moeen Riaz ◽  
Andrew Bakshi ◽  
Galina Polekhina ◽  
Le TP Thao ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Older People ◽  
Risk Score ◽  
Controlled Trial ◽  
Adult Population ◽  
Previous History ◽  
Polygenic Risk Score ◽  
Conventional Model ◽  
Polygenic Risk

Background: The use of a polygenic risk score (PRS) to predict coronary heart disease (CHD) events has been demonstrated in the general adult population. However, whether predictive performance extends to older individuals is unclear. Aim: To evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of individuals aged 70 years and older. Methods: We used data from 12,792 genotyped participants of the ASPREE trial, a randomized placebo-controlled trial investigating the effect of daily 100mg aspirin on disability-free survival in healthy older people. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrolment. We calculated a PRS comprising 1.7 million genetic variants (metaGRS). The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio 1.24 [95% confidence interval [CI] 1.08-1.42], p=0.002). The AUC of the conventional model was 70.53 (95%CI 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95%CI 68.32-75.24, p=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95%CI 0.15-0.28). Conclusions: A PRS for CHD performs well in older people, suggesting that the clinical utility of genomic risk prediction for CHD extends to this distinct high-risk subgroup.

scholarly journals Predictive Accuracy of a Polygenic Risk Score Compared With a Clinical Risk Score for Incident Coronary Heart Disease

JAMA ◽  
2020 ◽  
Vol 323 (7) ◽  
pp. 627 ◽  
Author(s):  
Jonathan D. Mosley ◽  
Deepak K. Gupta ◽  
Jingyi Tan ◽  
Jie Yao ◽  
Quinn S. Wells ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Predictive Accuracy ◽  
Polygenic Risk Score ◽  
Clinical Risk Score ◽  
Incident Coronary Heart Disease ◽  
Polygenic Risk ◽  
Clinical Risk

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

scholarly journals Polygenic Risk Score for Coronary Heart Disease Modifies the Elevated Risk by Cigarette Smoking for Disease Incidence

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
George Hindy ◽  
Frans Wiberg ◽  
Peter Almgren ◽  
Olle Melander ◽  
Marju Orho-Melander
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Risk Category ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Polygenic Risk ◽  
Never Smokers

Background: Coronary heart disease (CHD) is a multifactorial disease with both genetic and environmental components. Smoking is the most important modifiable risk factor for CHD. Our aim was to test whether the increased CHD incidence by smoking is modified by genetic predisposition to CHD. Methods and Results: Our study included 24 443 individuals from the MDCS (Malmö Diet and Cancer Study). A weighted polygenic risk score (PRS) was created by summing the number of risk alleles for 50 single-nucleotide polymorphisms associated with CHD. Individuals were classified as current, former, or never smokers. Interactions were primarily tested between smoking status and PRS and secondarily with individual single-nucleotide polymorphisms. Then, the predictive use of PRS for CHD incidence was tested among different smoking categories. During a median follow-up time of 19.4 years, 3217 incident CHD cases were recorded. The association between smoking and CHD was modified by the PRS ( P interaction =0.005). The magnitude of increased incidence of CHD by smoking was highest among individuals in the lowest tertile of PRS (odds ratio, 1.42; 95% confidence interval, 1.29–1.56 per smoking risk category) compared with the highest tertile (odds ratio, 1.20; 95% confidence interval, 1.11–1.30 per smoking risk category). This interaction was stronger among men ( P interaction =0.001) compared with women ( P interaction =0.44). The PRS provided a significantly better net reclassification and discrimination on top of traditional risk factors among never smokers compared with current smokers ( P <0.001). Conclusions: Genetic predisposition to CHD modifies the associated increased CHD risk by smoking. The PRS has a better predictive use among never smokers compared with smokers.

scholarly journals Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older

2021 ◽  
Author(s):  
Johannes T. Neumann ◽  
Moeen Riaz ◽  
Andrew Bakshi ◽  
Galina Polekhina ◽  
Le T.P. Thao ◽  
...  
Keyword(s):  
Risk Score ◽  
Cardiovascular Events ◽  
Prognostic Value ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Older Individuals ◽  
Conventional Model ◽  
Polygenic Risk ◽  
History Of ◽  
Genomic Risk

Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. Methods: We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08–1.42], P =0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00–74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32–75.24, P =0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15–0.28). Conclusion: A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583

1645-P: Polygenic Risk Score for Prediction of Complications in Men and Women with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1645-P
Author(s):  
JOHANNE TREMBLAY ◽  
REDHA ATTAOUA ◽  
MOUNSIF HALOUI ◽  
RAMZAN TAHIR ◽  
CAROLE LONG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Men And Women ◽  
Polygenic Risk ◽  
Prediction Of Complications

304-OR: Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
MICHAEL L. MULTHAUP ◽  
RYOSUKE KITA ◽  
NICHOLAS ERIKSSON ◽  
STELLA ASLIBEKYAN ◽  
JANIE SHELTON ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Diabetes Susceptibility ◽  
Genetic Database ◽  
Polygenic Risk

P4-240: Using polygenic risk score to predict Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_19) ◽  
pp. P872-P872 ◽  
Author(s):  
Valentina Escott-Price ◽  
Rebecca Sims ◽  
Denise Harold ◽  
Maria Vronskaya ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk
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