scholarly journals Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1105
Author(s):  
Laurent C. A. M. Tellier ◽  
Jennifer Eccles ◽  
Nathan R. Treff ◽  
Louis Lello ◽  
Simon Fishel ◽  
...  
Keyword(s):  
Family Environment ◽  
Disease Risk ◽  
New Technology ◽  
Large Population ◽  
Current Method ◽  
Risk Scores ◽  
Adult Health ◽  
Health It ◽  
Ethical Considerations ◽  
Artery Disease

Machine learning methods applied to large genomic datasets (such as those used in GWAS) have led to the creation of polygenic risk scores (PRSs) that can be used identify individuals who are at highly elevated risk for important disease conditions, such as coronary artery disease (CAD), diabetes, hypertension, breast cancer, and many more. PRSs have been validated in large population groups across multiple continents and are under evaluation for widespread clinical use in adult health. It has been shown that PRSs can be used to identify which of two individuals is at a lower disease risk, even when these two individuals are siblings from a shared family environment. The relative risk reduction (RRR) from choosing an embryo with a lower PRS (with respect to one chosen at random) can be quantified by using these sibling results. New technology for precise embryo genotyping allows more sophisticated preimplantation ranking with better results than the current method of selection that is based on morphology. We review the advances described above and discuss related ethical considerations.

Family Environment and Its Correlation with Anxiety and Depression: A Study on Heart Patients

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Dr. Meena Jain ◽  
Saloni Chandalia
Keyword(s):  
Heart Disease ◽  
Family Environment ◽  
Heart Attack ◽  
Psychiatric Symptoms ◽  
Disease Risk ◽  
Positive Association ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Increased Risk ◽  
Artery Disease

This research paper deals with the Family Environment and its Correlation with Anxiety and Depression level among persons with Heart Disease. There had been a number of researches that investigated that ischemic heart disease patients who suffer significant anxiety have close to a 5-fold increased risk of experiencing frequent angina and those with depression have more than a 3-fold increased risk for these episodes. This observed link between psychiatric symptoms and angina underlines the importance of treating anxiety and depression in cardiac patients, according to study co author Dr Mark D Sullivan (University of Washington School of Medicine, Seattle). To gather the needed data, Hamilton Anxiety Scale and Becks Depression Inventory were used. As stated from literatures, for people with heart dysfunction, depression and anxiety can increase the risk of an adverse cardiac event such as a heart attack or blood clots. For people who do not have heart disease, depression and anxiety can also increase the risk of a heart attack and development of coronary artery disease. Researchers have also emphasized on the role of family psychosocial environment and its positive association with the Coronary Heart Disease risk.

scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2019 ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T Rämö ◽  
Nina J Mars ◽  
Sanni Söderlund ◽  
Christian Benner ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Cumulative Exposure ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractBackgroundHyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). Monogenic familial hypercholesterolemia associates with higher increase in CAD risk than expected from a single LDL-C measurement, likely due to lifelong cumulative exposure to high LDL-C. It remains unclear to what extent a high polygenic load of LDL-C or TG-increasing variants associates with increased CAD risk.Methods and ResultsWe derived polygenic risk scores (PRS) with ∼6M variants for LDL-C and TG with weights from a UK biobank-based genome-wide association study with ∼500K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the FINRISK cohort, and to CAD risk in 135 300 individuals (13 695 CAD cases) from the FinnGen project.In FINRISK, LDL-C ranged from 2.83 (95% CI 2.79-2.89) to 3.80 (3.72-3.88) and TG from 0.99 (0.95-1.01) to 1.52 (1.48-1.58) mmol/l between the lowest and highest 5% of the respective PRS distributions. The corresponding CAD prevalences ranged from 8.2% to 12.7% for the LDL-C PRS and from 8.2% to 12.1% for the TG PRS in FinnGen. Furthermore, CAD risk was 1.36-fold higher (OR, 95% CI 1.24-1.49) for the LDL-C PRS and 1.31-fold higher (1.20-1.44) for the TG PRS for those with the PRS >95th percentile vs those without. These estimates were only slightly attenuated when adjusting for a CAD PRS (OR 1.26 [95% CI 1.15-1.39] for LDL-C and 1.21 [1.10-1.32] for TG PRS).ConclusionsThe CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and mostly independent of a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing more direct guidance for clinical translation.

scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2020 ◽  
Vol 13 (2) ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T. Rämö ◽  
Nina J. Mars ◽  
Yu Fu ◽  
Jake Lin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

Background: Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. Methods: We derived polygenic risk scores (PRSs) with ≈6M variants separately for LDL-C and TG with weights from a UK Biobank–based genome-wide association study with ≈324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). Results: In FINRISK, median LDL-C was 3.39 (95% CI, 3.38–3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82–2.94) to 3.78 (95% CI, 3.71–3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18–1.20) mmol/L, ranging from 0.97 (95% CI, 0.94–1.00) to 1.55 (95% CI, 1.48–1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24–1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19–1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16–1.38] for LDL-C and 1.24 [95% CI, 1.13–1.36] for TG PRS). Conclusions: The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.

scholarly journals Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories

2020 ◽  
Author(s):  
Ricky Lali ◽  
Michael Chong ◽  
Arghavan Omidi ◽  
Pedrum Mohammadi-Shemirani ◽  
Ann Le ◽  
...  
Keyword(s):  
Rare Variant ◽  
Genetic Risk ◽  
Complex Disease ◽  
Rare Variants ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Considerable Proportion ◽  
Asian Populations ◽  
Artery Disease

ABSTRACTRare variants are collectively numerous and may underlie a considerable proportion of complex disease risk. However, identifying genuine rare variant associations is challenging due to small effect sizes, presence of technical artefacts, and heterogeneity in population structure. We hypothesized that rare variant burden over a large number of genes can be combined into predictive rare variant genetic risk score (RVGRS). We propose a novel method (RV-EXCALIBER) that leverages summary-level data from a large public exome sequencing database (gnomAD) as controls and robustly calibrates rare variant burden to account for the aforementioned biases. A RVGRS was found to strongly associate with coronary artery disease (CAD) in European and South Asian populations. Calibrated RVGRS capture the aggregate effect of rare variants through a polygenic model of inheritance, identifies 1.5% of the population with substantial risk of early CAD, and confers risk even when adjusting for known Mendelian CAD genes, clinical risk factors, and common variant gene scores.

scholarly journals Polygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk

2020 ◽  
Vol 126 (9) ◽  
pp. 1159-1177 ◽  
Author(s):  
Krishna G. Aragam ◽  
Pradeep Natarajan
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Clinical Utility ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Scores ◽  
Atherosclerotic Cardiovascular Disease ◽  
Artery Disease ◽  
Atherosclerotic Cardiovascular Disease Risk

An individual’s susceptibility to atherosclerotic cardiovascular disease is influenced by numerous clinical and lifestyle factors, motivating the multifaceted approaches currently endorsed for primary and secondary cardiovascular disease prevention. With growing knowledge of the genetic basis of atherosclerotic cardiovascular disease—in particular, coronary artery disease—and its contribution to disease pathogenesis, there is increased interest in understanding the potential clinical utility of a genetic predictor that might further refine the assessment and management of atherosclerotic cardiovascular disease risk. Rapid scientific and technological advances have enabled widespread genotyping efforts and dynamic research in the field of coronary artery disease genetic risk prediction. In this review, we describe how genomic analyses of coronary artery disease have been leveraged to create polygenic risk scores. We then discuss evaluations of the clinical utility of these scores, pertinent mechanistic insights gleaned, and practical considerations relevant to the implementation of polygenic risk scores in the health care setting.

scholarly journals Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases

2019 ◽  
Author(s):  
Scott C. Ritchie ◽  
Yingying Liu ◽  
Samuel A. Lambert ◽  
Shu Mei Teo ◽  
Petar Scepanovic ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Disease Risk ◽  
Therapeutic Potential ◽  
Association Studies ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Disease Biology ◽  
Genome Wide ◽  
Associated Proteins ◽  
Artery Disease

AbstractPolygenic risk scores (PRSs) capture the genetic architecture of common diseases by aggregating genome-wide genetic variation into a single score that reflects an individual’s disease risk. These present new opportunities to identify molecular pathways involved in disease pathogenesis. We performed association analysis between PRSs and 3,442 plasma proteins in 3,175 healthy individuals, identifying 48 proteins whose levels associated with PRSs for coronary artery disease, chronic kidney disease, or type 2 diabetes. Integrative analyses of human and mouse data to characterise these associations revealed a role for polygenic effects on several well-known causal disease proteins and identified promising novel targets for future follow-up. We found implicated PRS-associated genes were responsive to dietary intervention in mice and showed strong evidence of druggability in humans, consistent with PRS-associated proteins having therapeutic potential. Overall, our study provides a framework for polygenic association studies, demonstrating the power of PRSs to unravel novel disease biology.

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