PREDICTIVE PERFORMANCE OF A POLYGENIC RISK SCORE FOR CORONARY HEART DISEASE IN A HEALTHY ELDERLY POPULATION

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.

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

JAMA ◽

10.1001/jama.2019.21782 ◽

2020 ◽

Vol 323 (7) ◽

pp. 627 ◽

Cited By ~ 29

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

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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

Journal of Epidemiology & Community Health ◽

10.1136/jech-2020-214358 ◽

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.

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PREDICTIVE PERFORMANCE OF A POLYGENIC RISK SCORE FOR INCIDENT ISCHEMIC STROKE IN A HEALTHY OLDER POPULATION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)02829-1 ◽

2021 ◽

Vol 77 (18) ◽

pp. 1471

Author(s):

Johannes Neumann ◽

Moeen Riaz ◽

Andrew Bakshi ◽

Galina Polekhina ◽

Le Thao ◽

...

Keyword(s):

Ischemic Stroke ◽

Risk Score ◽

Predictive Performance ◽

Polygenic Risk Score ◽

Older Population ◽

Polygenic Risk

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

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.117.001856 ◽

2018 ◽

Vol 11 (1) ◽

Cited By ~ 6

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.

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Separating the genetics of childhood and adult obesity: a validation study of genetic scores for body mass index in adolescence and adulthood in the HUNT Study

Human Molecular Genetics ◽

10.1093/hmg/ddaa256 ◽

2020 ◽

Author(s):

Maria Brandkvist ◽

Johan Håkon Bjørngaard ◽

Rønnaug Astri Ødegård ◽

Bjørn Olav Åsvold ◽

George Davey Smith ◽

...

Keyword(s):

Childhood Obesity ◽

Life Course ◽

Risk Score ◽

Predictive Performance ◽

Polygenic Risk Score ◽

Age Group ◽

Adult Obesity ◽

Polygenic Risk ◽

Hunt Study ◽

Variance Explained

Abstract From a life-course perspective, genetic and environmental factors driving childhood obesity may have a lasting influence on health later in life. However, how obesity trajectories vary throughout the life-course remains unknown. Recently, Richardson et al. created powerful early life and adult gene scores for BMI in a comprehensive attempt to separate childhood and adult obesity. The childhood score was derived using questionnaire-based data administered to adults aged 40-69 regarding their relative body size at age 10, making it prone to recall and misclassification bias. We therefore attempted to validate the childhood and adult scores using measured BMI data in adolescence and adulthood among 66 963 individuals from the HUNT Study in Norway from 1963 to 2019. The predictive performance of the childhood score was better in adolescence and early adulthood while the predictive performance of the adult score was better in adulthood. In the age group 12-15.9 years, the variance explained by the childhood polygenic risk score was 6.7% versus 2.4% for the adult polygenic risk score. In the age group 24-29.9 years, the variance explained by the adult PRS was 3.9% versus 3.6% for the childhood PRS. Our findings support that genetic factors driving BMI differ at young age and in adulthood. Within the framework of multivariable Mendelian randomization, the validated childhood gene score can now be used to determine the consequence of childhood obesity on later disease.

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