scholarly journals Intronic variants in the long non-coding RNA CDKN2B-AS1 are strongly associated with the risk of coronary artery disease in the Northern Tribes of Tanzania

2020 ◽  
Vol 21 (1) ◽  
pp. 1-14
Author(s):  
Gokce Akan ◽  
Peter Kisenge ◽  
Tulizo Shemu Sanga ◽  
Erasto Mbugi ◽  
Mehmet Kerem Turkcan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Sub Saharan Africa ◽  
Risk Haplotype ◽  
Genome Wide Association Studies ◽  
Marker Haplotype ◽  
Northern Tanzania ◽  
Artery Disease

Introduction: Sub-Saharan Africa (SSA) is facing a rising epidemic of non-communicable diseases including the coronary artery disease (CAD) ranking at the top of the list. Chromosome locus 9p21.3 containing CDKN2B antisense RNA 1 (CDKN2B-AS1), identified in many genome-wide association studies for coronary artery disease (CAD), encompasses multiple single nucleotide polymorphisms (SNPs). This study aimed to conduct the first genetic study evaluating the common polymorphisms in 9p21.3 locus in Tanzanian CAD patients from different regions of Tanzania and their associations with CAD risk factors. Material and Methods: A total of 90 patients from Northern region (N-CAD) of Tanzania and 65 patients from other regions (South, East, West and Central) (R-CAD) were included in the study. Further the biochemical analysis the genotyping of common variants was performed with the LightSNiP typing assay using qRT-PCR method.  Results: Our analyses revealed that both genotype and allele frequencies of rs10757274, rs10757278 and rs10811656 were significantly different between the groups (p<0.05, respectively). We identified that one previously undescribed three-marker haplotype (rs1333049, rs10757274 and rs10757278) encompassing CDKN2B-AS1 was overrepresented (G-G-G, the risk haplotype, p<0.05) in N-CAD group compared to R-CAD group. The AUC of a risk model based on non-genetic factors was 0.730 (0.654-0.797) and the combination with genetic risk factors improved the AUC to 0.784 (95%CI=0.713-0.844, p<0.0001). Conclusion: Our results identified the presence of a novel three-marker haplotype having a significant association with CAD in Northern Tanzania. Moreover, combination of the nongenetic and genetic risk models were demonstrated to indicate good diagnostic accuracy for CAD in Northern Tanzania.

Personalized management of coronary artery disease

ESC CardioMed ◽  
2018 ◽  
pp. 2989-2991
Author(s):  
Thorsten Kessler ◽  
Heribert Schunkert
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Coronary Atherosclerosis ◽  
Treatment Strategies ◽  
Integrated Approach ◽  
Genetic Risk Factors ◽  
Research Field ◽  
Artery Disease

Coronary artery disease and myocardial infarction are main causes of morbidity and mortality. In the past decades, several modifiable and non-modifiable risk factors underlying the disease have been identified. Recently, genome-wide association studies and next generation sequencing led to the discovery of genetic risk factors. Knowledge of these genetic risk factors has been shown to help to understand the pathophysiology of coronary atherosclerosis. Their knowledge might also be useful in risk prediction and diagnostics. Ultimately, an integrated approach using genetic information and novel imaging technologies should improve treatment strategies towards a personalized medicine. Here, we want to summarize recent findings in this research field and provide insight how these developments could be used to improve prevention and treatment of coronary atherosclerosis and its sequelae.

P4455The controversial role of genetics behind premature CAD: a plausible excuse for the young?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Sousa ◽  
M Mendonca ◽  
A Pereira ◽  
F Mendonca ◽  
M Neto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Young Patients ◽  
Premature Cad ◽  
Artery Disease ◽  
Group B

Abstract Introduction The complex interaction between genes and environmental factors contribute to individual-level risk of coronary artery disease (CAD), often resulting in premature CAD. The role for genetic risk scores in premature CAD is still controversial. Objective To evaluate the importance of conventional risk factors and of a genetic risk score in younger and older patients with coronary artery disease Methods From a group of 1619 pts with angiographic documented CAD from the GENEMACOR study, we selected 1276 pts admitted for ACS and analysed them in 2 groups (group A: ≤50 years, n=491 pts, 87.2% male, mean age 44±4.9 and group B: >50 years, n=785 pts, 75.2% male, mean age 57±4.2). Univariate analysis was used to characterize the traits of each group and we used ROC curves and respective AUCs to evaluate the power of genetics in the prediction of CAD, through a Genetic Risk Score (GRS). Results 99.3% of the young patients had at least one modifiable risk factor, 18.4% had 2 modifiable risk factors and 75.2% had 3 or more modifiable risk factors. The pattern of risk factors contributing to CAD were different among groups: family history (A: 27.5%, B: 21.4%, p=0.015) and smoking habits (A: 64.8%, B: 42.9%, p<0.001) were more frequent among patients under 50, and traditional age-linked factors like hypertension (A: 58%, B: 75.7%, p<0.001), diabetes (A: 21.6%, B: 38.6%, p<0.001) were more common in the older group. Acute ST-elevation myocardial infarction was more frequent among the young (A: 55.4%, B: 47.4%, p=0.006), as non-ST clinical presentation was higher among elder patients. Regarding angiographic presentation, single vessel CAD was higher in group A (A: 50.3%, B: 40.9%, p<0.001), while multivessel diasease was higher in group B (A: 33.3%, B: 53.9%, p<0.001). At a mean follow-up of 5 years, older patients had a worst prognosis, registering a higher rate of cardiovascular death (A: 4.1%, B: 8.6%, p=0.002) and higher MACE (A: 26.8%, B: 31%, p=0.128),. Adding the genetic risk score (GRS), we achieved only a slight improvement in the AUC for predicting CAD (0.796->0.805, p=0.0178 and 0.748->0.761, p=0.0007 in patients under and over 50, respectively). Conclusion Coronary artery disease is not all the same, as premature CAD shares a unique and specific pattern of risk factors, clinical presentation, angiographic severity and prognosis. Genetics should not be used as an excuse to justify premature CAD, as there is frequently more than one potentially reversible risk factor present even in young patients and the additive predictive value of GRS is modest.

scholarly journals Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease

2019 ◽  
Author(s):  
Jessica Dennis ◽  
Julia Sealock ◽  
Rebecca T. Levinson ◽  
Eric Farber-Eger ◽  
Jacob Franco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Major Depressive Disorder ◽  
Coronary Artery ◽  
Genetic Risk ◽  
European Ancestry ◽  
Major Depressive ◽  
Polygenic Score ◽  
Polygenic Scores ◽  
Artery Disease

AbstractMajor depressive disorder (MDD) and loneliness are phenotypically and genetically correlated with coronary artery disease (CAD), but whether these associations are explained by pleiotropic genetic variants or shared comorbidities is unclear. To tease apart these scenarios, we first assessed the medical morbidity pattern associated with genetic risk factors for MDD and loneliness by conducting a phenome-wide association study in 18,385 European-ancestry individuals in the Vanderbilt University Medical Center biobank, BioVU. Polygenic scores for MDD and loneliness were developed for each person using previously published meta-GWAS summary statistics, and were tested for association with 882 clinical diagnoses ascertained via billing codes in electronic health records. We discovered strong associations with heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 controls. We found odds ratios of 1.11 (95% CI, 1.04–1.18; P 8.43 × 10−4) and 1.13 (95% CI, 1.07–1.20; P 4.51 × 10−6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Results were similar in patients without psychiatric symptoms, and the increased risk persisted in females even after adjusting for multiple conventional risk factors and a polygenic score for CAD. In a final sensitivity analysis, we statistically adjusted for the genetic correlation between MDD and loneliness and re-computed polygenic scores. The polygenic score unique to loneliness remained associated with CAD (OR 1.09, 95% CI 1.03–1.15; P 0.002), while the polygenic score unique to MDD did not (OR 1.00, 95% CI 0.95–1.06; P 0.97). Our replication sample was the Atherosclerosis Risk in Communities (ARIC) cohort of 7197 European-ancestry participants (1598 incident CAD cases). In ARIC, polygenic scores for MDD and loneliness were associated with hazard ratios of 1.07 (95% CI, 0.99–1.14; P = 0.07) and 1.07 (1.01–1.15; P = 0.03), respectively, and we replicated findings from the BioVU sensitivity analyses. We conclude that genetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in females.

Prevalence of genetic risk factors for coronary artery disease in Corsica island (France)

2005 ◽  
Vol 79 (3) ◽  
pp. 210-213 ◽  
Author(s):  
A. Falchi ◽  
L. Giovannoni ◽  
I.S. Piras ◽  
C.M. Calo ◽  
P. Moral ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Artery Disease

scholarly journals Coronary artery disease, genetic risk and the metabolome in young individuals

2018 ◽  
Vol 3 ◽  
pp. 114 ◽  
Author(s):  
Thomas Battram ◽  
Luke Hoskins ◽  
David A. Hughes ◽  
Johannes Kettunen ◽  
Susan M. Ring ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Artery Disease

Background: Genome-wide association studies have identified genetic variants associated with coronary artery disease (CAD) in adults – the leading cause of death worldwide. It often occurs later in life, but variants may impact CAD-relevant phenotypes early and throughout the life-course. Cohorts with longitudinal and genetic data on thousands of individuals are letting us explore the antecedents of this adult disease. Methods: 149 metabolites, with a focus on the lipidome, measured using nuclear magnetic resonance (1H-NMR) spectroscopy, and genotype data were available from 5,905 individuals at ages 7, 15, and 17 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Linear regression was used to assess the association between the metabolites and an adult-derived genetic risk score (GRS) of CAD comprising 146 variants. Individual variant-metabolite associations were also examined. Results: The CAD-GRS associated with 118 of 149 metabolites (false discovery rate [FDR] < 0.05), the strongest associations being with low-density lipoprotein (LDL) and atherogenic non-LDL subgroups. Nine of 146 variants in the GRS associated with one or more metabolites (FDR < 0.05). Seven of these are within lipid loci: rs11591147 PCSK9, rs12149545 HERPUD1-CETP, rs17091891 LPL, rs515135 APOB, rs602633 CELSR2-PSRC1, rs651821 APOA5, rs7412 APOE-APOC1. All associated with metabolites in the LDL or atherogenic non-LDL subgroups or both including aggregate cholesterol measures. The other two variants identified were rs112635299 SERPINA1 and rs2519093 ABO. Conclusions: Genetic variants that influence CAD risk in adults are associated with large perturbations in metabolite levels in individuals as young as seven. The variants identified are mostly within lipid-related loci and the metabolites they associated with are primarily linked to lipoproteins. This knowledge could allow for preventative measures, such as increased monitoring of at-risk individuals and perhaps treatment earlier in life, to be taken years before any symptoms of the disease arise.

scholarly journals Coronary artery disease, genetic risk and the metabolome in young individuals

2019 ◽  
Vol 3 ◽  
pp. 114 ◽  
Author(s):  
Thomas Battram ◽  
Luke Hoskins ◽  
David A. Hughes ◽  
Johannes Kettunen ◽  
Susan M. Ring ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Artery Disease

Background: Genome-wide association studies have identified genetic variants associated with coronary artery disease (CAD) in adults – the leading cause of death worldwide. It often occurs later in life, but variants may impact CAD-relevant phenotypes early and throughout the life-course. Cohorts with longitudinal and genetic data on thousands of individuals are letting us explore the antecedents of this adult disease. Methods: 148 metabolites, with a focus on the lipidome, measured using nuclear magnetic resonance (1H-NMR) spectroscopy, and genotype data were available from 5,907 individuals at ages 7, 15, and 17 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Linear regression was used to assess the association between the metabolites and an adult-derived genetic risk score (GRS) of CAD comprising 146 variants. Individual variant-metabolite associations were also examined. Results: The CAD-GRS associated with 118 of 148 metabolites (false discovery rate [FDR] < 0.05), the strongest associations being with low-density lipoprotein (LDL) and atherogenic non-LDL subgroups. Nine of 146 variants in the GRS associated with one or more metabolites (FDR < 0.05). Seven of these are within lipid loci: rs11591147 PCSK9, rs12149545 HERPUD1-CETP, rs17091891 LPL, rs515135 APOB, rs602633 CELSR2-PSRC1, rs651821 APOA5, rs7412 APOE-APOC1. All associated with metabolites in the LDL or atherogenic non-LDL subgroups or both including aggregate cholesterol measures. The other two variants identified were rs112635299 SERPINA1 and rs2519093 ABO. Conclusions: Genetic variants that influence CAD risk in adults are associated with large perturbations in metabolite levels in individuals as young as seven. The variants identified are mostly within lipid-related loci and the metabolites they associated with are primarily linked to lipoproteins. Along with further research, this knowledge could allow for preventative measures, such as increased monitoring of at-risk individuals and perhaps treatment earlier in life, to be taken years before any symptoms of the disease arise.

scholarly journals Validation of eight genetic risk factors in East Asian populations replicated the association of BRAP with coronary artery disease

2009 ◽  
Vol 54 (11) ◽  
pp. 642-646 ◽  
Author(s):  
Kunihiko Hinohara ◽  
Hitoshi Ohtani ◽  
Toshiaki Nakajima ◽  
Taishi Sasaoka ◽  
Motoji Sawabe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
East Asian ◽  
Genetic Risk Factors ◽  
Asian Populations ◽  
Artery Disease

scholarly journals Moving Beyond Clinical Risk Scores with a Mobile App for the Genomic Risk of Coronary Artery Disease

2017 ◽  
Author(s):  
Evan D. Muse ◽  
Nathan E. Wineinger ◽  
Brian Schrader ◽  
Bhuvan Molparia ◽  
Emily G. Spencer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Primary Prevention ◽  
Statin Therapy ◽  
Genetic Risk ◽  
Healthy Lifestyle ◽  
Mobile App ◽  
Clinical Risk ◽  
Artery Disease

SUMMARYPrimary prevention of coronary artery disease (CAD) is important for individuals at increased risk, and largely consists of healthy lifestyle modifications and initiation of medications when appropriate – including statins. Defining the inherent risk for any given individual typically relies on traditional risk factors established decades ago by the Framingham Heart Study. Unfortunately, recent studies have indicated that these traditional clinical risk factors systematically overestimate the risk of CAD across all major ancestries. This has increased the number of patients that would be eligible for statin therapy for the primary prevention of CAD but would likely receive little benefit and potentially incur negative consequences. On the other hand, researchers have demonstrated that genetic factors can effectively identify a subset of high risk individuals, and that the benefit from statin therapy is greatest among individuals with the highest genetic risk score (GRS). These individuals also receive the greatest absolute benefit from healthy lifestyle choices, being able to titrate their risk to normal levels despite high genetic predisposition. However, it is not yet possible for the average individual to discover their genetic risk because no tools are currently available to make such a determination. Here, we present a free mobile app – MyGeneRank – that can provide this information. Individuals may choose to use this knowledge to complement traditional risk assessments, and make critical decisions regarding lifelong statin therapy and lifestyle changes. As of 1/25/2017, MyGeneRank is currently in closed beta and will soon be available to the public.

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