scholarly journals Sexual Differences in Genetic Predisposition of Coronary Artery Disease

2020 ◽  
Author(s):  
Yunfeng Huang ◽  
Qin Hui ◽  
Marta Gwinn ◽  
Yi-Juan Hu ◽  
Arshed A. Quyyumi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Men And Women ◽  
High Genetic Risk ◽  
Genome Wide ◽  
Artery Disease

Background - The genomic structure that contributes to the risk of coronary artery disease (CAD) can be evaluated as a risk score of multiple variants. However, sex differences have not been fully examined in applications of genetic risk score of CAD. Methods - Using data from the UK Biobank, we constructed a CAD genetic risk score based on all known loci, three mediating trait-based (blood pressure, lipids, body mass index) sub-scores, and a genome-wide polygenic risk score based on 1.1 million variants. The differences in genetic associations with prevalent and incident CAD between men and women were investigated among 317,509 unrelated individuals of European ancestry. We also assessed interactions with sex for 161 individual loci included in the comprehensive genetic risk score. Results - For both prevalent and incident CAD, the associations of comprehensive and genome-wide genetic risk scores were stronger among men than women. Using a score of 161 loci, we observed a 2.4 times higher risk for incident CAD comparing men with high genetic risk to men with low genetic risk, but an 80 percent greater risk comparing women with high genetic risk to women with low genetic risk. (interaction p=0.002). Of the three sub-scores, the blood pressure-associated sub-score exhibited sex differences (interaction p=0.0004 per SD increase in sub-score). Analysis of individual variants identified a novel gene-sex interaction at locus 21q22.11 . Conclusions - Sexual differences in genetic predisposition should be considered in future studies of coronary artery disease, and genetic risk scores should not be assumed to perform equally well in men and women.

scholarly journals Polygenic risk for coronary artery disease in the Scottish and English population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuhua Yang ◽  
Fabian Starnecker ◽  
Shichao Pang ◽  
Zhifen Chen ◽  
Ulrich Güldener ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Individual Risk ◽  
Risk Alleles ◽  
Genome Wide ◽  
Artery Disease ◽  
Cad Risk

Abstract Background Epidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon. Methods Using UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk. Results Prevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each). Conclusions Neither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.

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.

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease

2017 ◽  
Vol 71 (6) ◽  
pp. e12956 ◽  
Author(s):  
Andreia Pereira ◽  
Maria Isabel Mendonca ◽  
Ana Célia Sousa ◽  
Sofia Borges ◽  
Sónia Freitas ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Cardiovascular Mortality ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
European Population ◽  
Artery Disease

ISH NIA PS 03-06 Genetic risk score determines cardiovascular complications in patients with stable coronary artery disease

2016 ◽  
Vol 34 (Supplement 1) ◽  
pp. e282
Author(s):  
Marcin Wirtwein ◽  
Olle Melander ◽  
Marketa Sjogren ◽  
Michal Hoffmann ◽  
Krzysztof Narkiewicz ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Stable Coronary Artery Disease ◽  
Cardiovascular Complications ◽  
Artery Disease
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