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

scholarly journals Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia

2015 ◽  
Vol 72 (7) ◽  
pp. 635 ◽  
Author(s):  
Esben Agerbo ◽  
Patrick F. Sullivan ◽  
Bjarni J. Vilhjálmsson ◽  
Carsten B. Pedersen ◽  
Ole Mors ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Family History ◽  
Psychiatric Disorders ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
History Of ◽  
Parental Socioeconomic Status

scholarly journals Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population

2020 ◽  
Author(s):  
Moeen Riaz ◽  
Aamira Huq ◽  
Joanne Ryan ◽  
Suzanne G Orchard ◽  
Jane Tiller ◽  
...  
Keyword(s):  
Relative Risk ◽  
Cognitive Decline ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Genetic Factors ◽  
Polygenic Risk Score ◽  
Older Individuals ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Incidence Of Dementia

AbstractImportanceFew studies have measured the effect of genetic factors on dementia and cognitive decline in a population of healthy older individuals followed prospectively.ObjectiveTo examine the effect of Apolipoprotein E (APOE) genotypes and a polygenic risk score (PRS) on incident dementia and cognitive decline in a longitudinal cohort of healthy older people.Design, Setting and ParticipantsPost-hoc genetic analysis of a randomized clinical trial population - the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrollment, participants had no history of diagnosed dementia, atherothrombotic cardiovascular disease, or permanent physical disability and were without cognitive impairment.Main Outcomes and MeasuresDementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence curves for all-cause dementia and cognitive decline were calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants.Results12,978 participants with European ancestry were included; 54.8% were female, and average age at baseline was 75 years (range 70 to 96). During a median 4.5 years of follow-up, 324 (2.5%) participants developed dementia and 503 (3.8%) died. Cumulative incidence of dementia to age 85 years was estimated to be 7.4% in all participants, 12.6% in APOE ε4 heterozygotes, 26.6% in ε4 homozygotes, 9.6% in the high PRS tertile, and 7.3% in the low PRS tertile. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased risk of dementia and a 1.4/1.8-fold increased risk of cognitive decline, versus ε3/ε3 (P<0.001 for both). A high PRS (top tertile) was associated with a 1.4-fold increase risk of dementia, versus the low tertile (CI 1.04-1.76, P=0.02), but was not associated with cognitive decline risk (CI 0.96-1.22, P = 0.18).Conclusions and RelevanceIncidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.KEY POINTSQuestionHow do genetic factors influence the risk of dementia and cognitive decline among healthy older individuals?FindingsWe studied cumulative incidence of dementia and cognitive decline in 12,978 healthy older individuals without cardiovascular disease or cognitive impairment at enrollment, stratified by APOE genotype and a polygenic risk score (PRS). APOE ε4 and PRS increased the relative risk of dementia, but cumulative incidence was low across all genotypes. APOE genotypes were associated with cognitive decline, but PRS was not.MeaningIncidence of dementia is low among healthy older individuals; however, genetic factors still increase relative risk.

The Polygenic Risk Score of Subjective Well-Being, Self-Employment, and Earnings Among Older Individuals

2020 ◽  
pp. 104225872093698 ◽  
Author(s):  
Pankaj C. Patel ◽  
Cornelius A. Rietveld ◽  
Marcus T. Wolfe ◽  
Johan Wiklund
Keyword(s):  
Risk Score ◽  
Positive Association ◽  
Well Being ◽  
Polygenic Risk Score ◽  
Subjective Well Being ◽  
Older Individuals ◽  
Polygenic Risk ◽  
Self Employment ◽  
Time Invariant ◽  
Weighted Combination

We investigate whether the polygenic risk score (PRS) of subjective well-being (SWB), a weighted combination of multiple genetic variants which captures an individual’s time-invariant genetic predisposition to SWB, influences the choice of self-employment and whether it explains differences in earnings between older self-employed and employed workers. In a sample of 4,571 individuals (50 to 65 years old) representing 14,937 individual-year observations from the Health and Retirement Study, we find that the PRS of SWB is positively associated with self-employment and earnings. However, contrary to our expectations, the positive association with earnings is not significantly different between self-employed and employed individuals.

Mo1615 POTENTIAL CLINICAL UTILITY OF SNP-BASED POLYGENIC RISK SCORE FOR DEVELOPING PERSONALIZED COLONOSCOPY SCREENING STRATEGY

2020 ◽  
Vol 158 (6) ◽  
pp. S-917
Author(s):  
Michael J. Northcutt ◽  
Michael K. Zijlstra ◽  
Ayush N. Shah ◽  
Mohammad Beig ◽  
Polina Imas ◽  
...  
Keyword(s):  
Risk Score ◽  
Clinical Utility ◽  
Screening Strategy ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Colonoscopy Screening ◽  
Potential Clinical Utility

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.

Polygenic Risk Score Predicts Cardiovascular Events in Familial Hypercholesterolemia

2017 ◽  
Vol 11 (3) ◽  
pp. 787-788
Author(s):  
Alexis Baass ◽  
Martine Paquette ◽  
Michael Chong ◽  
Sébastien Thériault ◽  
Robert Dufour ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Risk Score ◽  
Cardiovascular Events ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Scores polygéniques et risque de cancer

2020 ◽  
Vol 36 (5) ◽  
pp. 535-537
Author(s):  
Bertrand Jordan
Keyword(s):  
Risk Assessment ◽  
Risk Score ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Cancer Type ◽  
Polygenic Risk

Risk assessment for a cancer type with moderate heritability can be accurately performed using a relatively small number of SNPs detected by GWAS analyses to calculate a polygenic risk score (PRS) that has definite clinical utility.

Polygenic risk score as clinical utility in psychiatry: a clinical viewpoint

2020 ◽  
Vol 66 (1) ◽  
pp. 53-60
Author(s):  
Masashi Ikeda ◽  
Takeo Saito ◽  
Tetsufumi Kanazawa ◽  
Nakao Iwata
Keyword(s):  
Risk Score ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals A polygenic risk score to predict future adult short stature amongst children

2021 ◽  
Author(s):  
Tianyuan Lu ◽  
Vincenzo Forgetta ◽  
Haoyu Wu ◽  
John R B Perry ◽  
Ken K Ong ◽  
...  
Keyword(s):  
Short Stature ◽  
Risk Score ◽  
Clinical Utility ◽  
Adult Height ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Parental Height ◽  
The Uk

Abstract Context Adult height is highly heritable, yet no genetic predictor has demonstrated clinical utility compared to mid-parental height. Objective To develop a polygenic risk score for adult height and evaluate its clinical utility. Design A polygenic risk score was constructed based on meta-analysis of genome-wide association studies and evaluated on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Subjects Participants included 442,599 genotyped White British individuals in the UK Biobank, and 941 genotyped child-parent trios of European ancestry in the ALSPAC cohort. Interventions None. Main Outcome Measures Standing height was measured using stadiometer; Standing height two standard deviations below the sex-specific population average was considered as short stature. Results Combined with sex, a polygenic risk score captured 71.1% of the total variance in adult height in the UK Biobank. In the ALSPAC cohort, the polygenic risk score was able to identify children who developed adulthood short stature with an area under the receiver operating characteristic curve (AUROC) of 0.84, which is close to that of mid-parental height. Combining this polygenic risk score with mid-parental height, or only one of the child’s parent’s height, could improve the AUROC to at most 0.90. The polygenic risk score could also substitute mid-parental height in age-specific Khamis-Roche height predictors and achieve an equally strong discriminative power in identifying children with a short stature in adulthood. Conclusions A polygenic risk score could be considered as an alternative or adjunct to mid-parental height to improve screening for children at risk of developing short stature in adulthood in European ancestry populations.

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