Genetic Risk Stratification

Roberts, Robert; Chang, Cheng-Chieh; Hadley, Trevor

doi:10.1016/j.jacbts.2020.09.004

Cited by 23 publications

(18 citation statements)

References 135 publications

(101 reference statements)

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“…For example, we can encourage an individual with high genetic risk of coronary artery disease (CAD) to adopt healthy life style and engage regular physical exams (Roberts et al, 2021), with studies showing that lifestyle factors and genetic factors have independent effects on CAD (Ye et al, 2021). In addition, regular physical exams may help detect CAD early (Johnson et al, 2004), and early therapy can reduce the incidence of CAD (Domanski et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Estimating genetic architecture and integrating functional annotations improve polygenic risk scores derived from GWAS summary statistics

Zhao,

Jiang,

Girgenti

2023

Preprint

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Constructing accurate polygenic risk scores (PRS) can benefit the prevention and early treatment of complex diseases. This can be accomplished by leveraging different information characterizing the effects of genetic variants on the diseases, and incorporating functional annotations. In this article, we propose a Genome-Wide Empirical Bayes (GWEB) method to first estimate the genetic architecture with the consideration of linkage disequilibrium (LD) among the genetic variants, and utilize the estimates to improve PRS derived from GWAS summary statistics. Our method further incorporates functional annotations to improve prediction accuracy. No parameters need to be tuned with other individual-level GWAS data. Extensive simulations showed that GWEB outperformed existing methods in different genetic architecture scenarios. Real data applications on six quantitative traits and six binary diseases demonstrated that, without functional annotations, GWEB can achieve 0.1-24% (average: 7%) relative improvement in terms of predictive r2 over the best performance of seven existing methods. Moreover, compared to the existing method using annotation information, GWEB can achieve 3-58% (average: 12%) relative improvement after integrating 120 functional annotations. The prediction model can be built within 1.2h and 40G memory after parallelized on 22 Intel Xeon cores.

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Section: Discussionmentioning

confidence: 99%

Estimating genetic architecture and integrating functional annotations improve polygenic risk scores derived from GWAS summary statistics

Zhao,

Jiang,

Girgenti

2023

Preprint

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“…Image Credit: American College of Lifestyle Medicine quantified by Polygenic Risk Scores (PRS). 221 Among the UK Biobank participants, individuals with high cardiorespiratory fitness showed 43% lower risk of CHD, despite high PRS. 222 From another analysis of the UK Biobank, it was noted that in the setting of high genetic risk, unfavorable lifestyle, compared to favorable lifestyle increased the risk of stroke by 66%.…”

Section: Genetic Risk Of Cardiovascular Disease and Lifestylementioning

confidence: 99%

Lifestyle Medicine: An Antidote to Cardiovascular Diseases

Reddy

Freeman

2022

American Journal of Lifestyle Medicine

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Despite numerous advances in basic understanding of cardiovascular disease pathophysiology, pharmacology, therapeutic procedures, and systems improvement, there hasn’t been much decline in heart disease related morality in the US since 2010. Hypertension and diet induced risk continue to be the leading causes of cardiovascular morbidity. Even with the excessive mortality associated with the COVID-19 pandemic, in 2020, heart disease remained the leading cause of death. Given the degree of disease burden, morbidity, and mortality, there is an urgent need to redirect medical professionals’ focus towards prevention through simple and cost effective lifestyle strategies. However, current practice paradigm and financial compensation systems are mainly centered disease management and not health promotion. For example, the financial value placed on 3–10 min smoking cessation counseling (.24RVUs) is 47-fold lower than an elective PCI (11.21 RVUs). The medical community seems to be enamored with the latest and greatest technology, new devices, and surgical procedures. What if the greatest technology of all was simply the way we live every day? Perhaps when this notion is known by enough, we will switch to this lifestyle medicine technology to prevent disease in the first place.

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“…Considering this genetic complexity, numerous studies have focused on identifying associations between genetic variants and common cardiovascular disease traits ( 15 , 18 – 21 ). This has been supported with the establishment of genome wide association studies (GWAS), which employ technologies that detect many gene variants simultaneously ( 22 ). The predominant variants identified through GWAS are single nucleotide polymorphisms (SNPs) ( 15 , 22 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

“…This has been supported with the establishment of genome wide association studies (GWAS), which employ technologies that detect many gene variants simultaneously ( 22 ). The predominant variants identified through GWAS are single nucleotide polymorphisms (SNPs) ( 15 , 22 – 24 ). SNPs can be located within a protein-coding region, where they may display a functional effect, but they can also be in non-coding and regulatory areas of the genome (e.g., introns, enhancer, etc.).…”

Section: Introductionmentioning

confidence: 99%

VEGF-A related SNPs: a cardiovascular context

Meza-Alvarado,

Page,

Mallard

et al. 2023

Front. Cardiovasc. Med.

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Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Currently, cardiovascular disease risk algorithms play a role in primary prevention. However, this is complicated by a lack of powerfully predictive biomarkers that could be observed in individuals before the onset of overt symptoms. A key potential biomarker for heart disease is the vascular endothelial growth factor (VEGF-A), a molecule that plays a pivotal role in blood vessel formation. This molecule has a complex biological role in the cardiovascular system due to the processes it influences, and its production is impacted by various CVD risk factors. Research in different populations has shown single nucleotide polymorphisms (SNPs) may affect circulating VEGF-A plasma levels, with some variants associated with the development of CVDs, as well as CVD risk factors. This minireview aims to give an overview of the VEGF family, and of the SNPs reported to influence VEGF-A levels, cardiovascular disease, and other risk factors used in CVD risk assessments.

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Genetic Risk Stratification

Cited by 23 publications

References 135 publications

Estimating genetic architecture and integrating functional annotations improve polygenic risk scores derived from GWAS summary statistics

Estimating genetic architecture and integrating functional annotations improve polygenic risk scores derived from GWAS summary statistics

Lifestyle Medicine: An Antidote to Cardiovascular Diseases

VEGF-A related SNPs: a cardiovascular context

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