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

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.

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Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

Psychological Medicine ◽

10.1017/s0033291717003087 ◽

2017 ◽

Vol 48 (9) ◽

pp. 1532-1539 ◽

Cited By ~ 8

Author(s):

E. Neilson ◽

C. Bois ◽

T.-K. Clarke ◽

L. Hall ◽

E. C. Johnstone ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Familial Risk ◽

Positive Association ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Score Analysis ◽

Increased Risk ◽

Heritable Disorder ◽

Diagnostic Symptoms

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

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Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration

Pharmaceuticals ◽

10.3390/ph13090257 ◽

2020 ◽

Vol 13 (9) ◽

pp. 257 ◽

Cited By ~ 1

Author(s):

Taiyo Shijo ◽

Yoichi Sakurada ◽

Seigo Yoneyama ◽

Wataru Kikushima ◽

Atsushi Sugiyama ◽

...

Keyword(s):

Macular Degeneration ◽

Risk Score ◽

Positive Association ◽

Age Related Macular Degeneration ◽

P Value ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Risk Variants ◽

Age Related ◽

One Year

We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10−4). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10−6). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD.

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

10.1101/2020.10.11.20210963 ◽

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.

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

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.121.003429 ◽

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

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