scholarly journals Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease

2021 ◽  
Author(s):  
Michael G. Levin ◽  
Derek Klarin ◽  
Venexia M. Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
Pulse Pressure ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Objective: We aimed to estimate the effect of blood pressure (BP) traits and BP-lowering medications (via genetic proxies) on peripheral artery disease. Approach and Results: Genome-wide association studies summary statistics were obtained for BP, peripheral artery disease (PAD), and coronary artery disease. Causal effects of BP on PAD were estimated by 2-sample Mendelian randomization using a range of pleiotropy-robust methods. Increased systolic BP (SBP), diastolic BP, mean arterial pressure (MAP), and pulse pressure each significantly increased risk of PAD (SBP odds ratio [OR], 1.20 [1.16–1.25] per 10 mm Hg increase, P =1×10 −24 ; diastolic BP OR, 1.27 [1.18–1.35], P =4×10 − 11 ; MAP OR, 1.26 [1.19–1.33], P =6×10 − 16 ; pulse pressure OR, 1.31 [1.24–1.39], P =9×10 − 23 ). The effects of SBP, diastolic BP, and MAP were greater for coronary artery disease than PAD (SBP ratio of Ors, 1.06 [1.0–1.12], P = 0.04; MAP ratio of OR, 1.15 [1.06–1.26], P =8.6×10 − 4 ; diastolic BP ratio of OR, 1.21 [1.08–1.35], P =6.9×10 − 4 ). Considered jointly, both pulse pressure and MAP directly increased risk of PAD (pulse pressure OR, 1.26 [1.17–1.35], P =3×10 − 10 ; MAP OR, 1.14 [1.06–1.23], P =2×10 − 4 ). The effects of antihypertensive medications were estimated using genetic instruments. SBP-lowering via β-blocker (OR, 0.74 per 10 mm Hg decrease in SBP [95% CI, 0.65–0.84]; P =5×10 − 6 ), loop diuretic (OR, 0.66 [0.48–0.91], P =0.01), and thiazide diuretic (OR, 0.57 [0.41–0.79], P =6×10 − 4 ) associated variants were protective of PAD. Conclusions: Higher BP is likely to cause PAD. BP-lowering through β blockers, loop diuretics, and thiazide diuretics (as proxied by genetic variants) was associated with decreased risk of PAD. Future study is needed to clarify the specific mechanisms by which BP influences PAD.

Identification of Phosphorylation Associated SNPs for Blood Pressure, Coronary Artery Disease and Stroke from Genome-wide Association Studies

2019 ◽  
Vol 19 (10) ◽  
pp. 731-738
Author(s):  
Xingchen Wang ◽  
Xingbo Mo ◽  
Huan Zhang ◽  
Yonghong Zhang ◽  
Yueping Shen
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Association Studies ◽  
Serum Levels ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Artery Disease

Purpose: Phosphorylation-related SNP (phosSNP) is a non-synonymous SNP that might influence protein phosphorylation status. The aim of this study was to assess the effect of phosSNPs on blood pressure (BP), coronary artery disease (CAD) and ischemic stroke (IS). Methods: We examined the association of phosSNPs with BP, CAD and IS in shared data from genome-wide association studies (GWAS) and tested if the disease loci were enriched with phosSNPs. Furthermore, we performed quantitative trait locus analysis to find out if the identified phosSNPs have impacts on gene expression, protein and metabolite levels. Results: We found numerous phosSNPs for systolic BP (count=148), diastolic BP (count=206), CAD (count=20) and IS (count=4). The most significant phosSNPs for SBP, DBP, CAD and IS were rs1801131 in MTHFR, rs3184504 in SH2B3, rs35212307 in WDR12 and rs3184504 in SH2B3, respectively. Our analyses revealed that the associated SNPs identified by the original GWAS were significantly enriched with phosSNPs and many well-known genes predisposing to cardiovascular diseases contain significant phosSNPs. We found that BP, CAD and IS shared for phosSNPs in loci that contain functional genes involve in cardiovascular diseases, e.g., rs11556924 (ZC3HC1), rs1971819 (ICA1L), rs3184504 (SH2B3), rs3739998 (JCAD), rs903160 (SMG6). Four phosSNPs in ADAMTS7 were significantly associated with CAD, including the known functional SNP rs3825807. Moreover, the identified phosSNPs seemed to have the potential to affect transcription regulation and serum levels of numerous cardiovascular diseases-related proteins and metabolites. Conclusion: The findings suggested that phosSNPs may play important roles in BP regulation and the pathological mechanisms of CAD and IS.

Recent success in the discovery of coronary artery disease genes

2011 ◽  
Vol 89 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Robert Roberts ◽  
Li Chen ◽  
George A. Wells ◽  
Alexandre F.R. Stewart
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Association Studies ◽  
Short Interval ◽  
Minimal Risk ◽  
Genome Wide Association Studies ◽  
Common Diseases ◽  
Multiple Genes ◽  
Increased Risk ◽  
Artery Disease

For more than 50 years, epidemiological studies have indicated that genetic predisposition accounts for approximately 50% of the susceptibility to coronary artery disease (CAD) and its sequelae, including myocardial infarction. Since common diseases such as CAD are caused by multiple genes, the age-old method of linkage analysis used to map monogenic Mendelian disorders in families unfortunately lacks the required sensitivity. The technology to identify genes predisposing individuals to CAD and other common diseases did not become available until 2005. This technology provided computerized arrays containing hundreds of thousands of DNA markers in the form of single-nucleotide polymorphisms (SNPs). This made it possible to pursue an unbiased approach referred to as genome-wide association studies. The first gene for CAD was simultaneously identified by 2 independent groups in 2007. In a very short interval, a total of 23 loci were mapped that were linked to increased risk for CAD. The results of these studies confirm that CAD is caused by multiple genes, each contributing minimal risk. The most exciting and novel findings are that these loci do not act through known risk factors for CAD and that the loci are more likely to be in DNA regions that regulate transcription rather than being in coding regions for protein.

scholarly journals Metabolic biomarkers for peripheral artery disease compared with coronary artery disease: Lipoprotein and metabolite profiling of 31,657 individuals from five prospective cohorts

2020 ◽  
Author(s):  
Emmi Tikkanen ◽  
Vilma Jägerroos ◽  
Rodosthenis Rodosthenous ◽  
Michael Holmes ◽  
Naveed Sattar ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Diseases ◽  
Peripheral Artery ◽  
Ldl Particles ◽  
Increased Risk ◽  
Artery Disease

Background: Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We conducted detailed metabolic profiling to identify biomarkers for the risk of developing PAD and compared with risk of CAD to explore common and unique risk factors for these different vascular diseases. Methods: We measured blood biomarkers using nuclear magnetic resonance metabolomics in five Finnish prospective general-population cohorts (FINRISK 1997, 2002, 2007, 2012, and Health 2000 studies, n = 31,657). We used Cox modelling to estimate associations between biomarkers and incident symptomatic PAD and CAD (498 and 2073 events, respectively) during median follow-up time of 14 years. Results: The pattern of biomarker associations for incident PAD deviated from that for CAD. Apolipoproteins and cholesterol measures were robustly associated with incident CAD (for example, age- and sex-adjusted hazard ratio per SD for higher apolipoprotein B/A 1 ratio: 1.30; 95% confidence interval 1.25-1.36), but not with incident PAD (1.04; 0.95-1.14; Pheterogeneity < 0.001). Low-density lipoprotein (LDL) particle concentrations were also associated with incident CAD (e.g. small LDL particles: 1.24; 1.19-1.29) but not with PAD (1.07; 0.98-1.17; Pheterogeneity < 0.001). In contrast, more consistent associations of smaller LDL particle size and higher triglyceride levels in LDL and HDL particles with increased risk for both CAD and PAD events were seen (Pheterogeneity > 0.05). Many non-traditional biomarkers, including fatty acids, amino acids, inflammation- and glycolysis-related metabolites were associated with future PAD events. Lower levels of linoleic acid, an omega-6 fatty acid, and higher concentrations of glucose, lactate, pyruvate, glycerol and glycoprotein acetyls were more strongly associated with incident PAD as compared to CAD (Pheterogeneity < 0.001). The differences in metabolic biomarker associations for PAD and CAD remained when adjusting for body mass index, smoking, prevalent diabetes, and medications. Conclusions: The metabolic biomarker profile for future PAD risk is largely distinct from that of CAD. This may represent pathophysiological differences and may facilitate risk prediction.

scholarly journals Cis-epistasis at the LPA locus and risk of coronary artery disease

2019 ◽  
Author(s):  
Lingyao Zeng ◽  
Nazanin Mirza-Schreiber ◽  
Claudia Lamina ◽  
Stefan Coassin ◽  
Christopher P. Nelson ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Association Studies ◽  
Arterial Disease ◽  
Genome Wide Association Studies ◽  
Interaction Patterns ◽  
Cardiovascular Risks ◽  
Increased Risk ◽  
Artery Disease ◽  
Cad Risk

AbstractIdentification of epistasis affecting complex human traits has been challenging. Focusing on known coronary artery disease (CAD) risk loci, we explore pairwise statistical interactions between 8,068 SNPs from ten CAD genome-wide association studies (n=30,180). We discovered rs1800769 and rs9458001 in the vicinity of the LPA locus to interact in modulating CAD risk (P=1.75×10−13). Specific genotypes (e.g., rs1800769 CT) displayed either significantly decreased or increased risk for CAD in the context of genotypes of the respective other SNP (e.g., rs9458001 GG vs. AA). In the UK Biobank (n=450,112) significant interaction of this SNP pair was replicated for CAD (P=3.09×10−22), and was also found for aortic valve stenosis (P=6.95×10−7) and peripheral arterial disease (P=2.32×10−4). Identical interaction patterns affected circulating lipoprotein(a) (n=5,953; P=8.7×10−32) and hepatic apolipoprotein(a) (apo(a)) expression (n=522, P=2.6×10−11). We further interrogated potential biological implications of the variants and propose a mechanism explaining epistasis that ultimately may translate to substantial cardiovascular risks.

scholarly journals The SNP rs7865618 of 9p21.3 locus emerges as the most promising marker of coronary artery disease in the southern Indian population

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gorre Manjula ◽  
Rayabarapu Pranavchand ◽  
Irgam Kumuda ◽  
B. Sriteja Reddy ◽  
Battini Mohan Reddy
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Indian Population ◽  
Interaction Analysis ◽  
Association Studies ◽  
Specific Marker ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Artery Disease

AbstractDevelopment of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, however the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. Genome wide association studies revealed association of variants in this region with CAD pathology. However, specific marker in predicting CAD development or progression is not yet identified. In the present study, 35 SNPs at 9p21.3 region, located in the cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) genes, were genotyped among 350 CAD cases and 480 controls from the southern Indian population of Hyderabad using fluidigm nanofluidic SNP genotyping system and the data were analyzed using PLINK and R softwares. Of the 35 SNPs analysed, only one SNP, rs7865618, was found to be highly significantly associated with CAD, even after correction for multiple testing (p = 0.008). The AG and GG genotypes of this SNP conferred 3.08 and 1.93 folds increased risk for CAD respectively. In particular, this SNP was significantly associated with severe anatomic (triple vessel disease p = 0.023) and phenotypic (acute coronary syndrome p = 0.007) categories of CAD. Pair wise SNP interaction analysis between the SNPs of 9p21.3 and 11q23.3 regions revealed significantly increased risk of three SNPs of 11q23.3 region that were not associated individually, in conjunction with rs7865618 of 9p21.3.

scholarly journals An observational study of incidence and severity of coronary artery disease in peripheral artery disease patients in South India

2020 ◽  
Vol 8 (12) ◽  
pp. 4271
Author(s):  
Vijay Sai Chowdekar ◽  
Naveen Peddi
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
South India ◽  
Fisher Exact Test ◽  
Care Hospital ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Retrospective Clinical Study ◽  
Artery Disease

Background: There are many studies that have evaluated peripheral artery disease (PAD) using ankle brachial index. However, there is very little epidemiological data on angiographically diagnosed PAD and its association with definite coronary artery disease (CAD) in Indians. The aim of this study is to evaluate the relationship between PAD and CAD in South Indian patients.  Methods: This was an observational, descriptive, single-arm, single-centre, retrospective clinical study. The study included 111 patients with known PAD who were admitted to a tertiary care hospital in South India. Patients with PAD by history, clinical examination, and those who underwent peripheral as well as coronary angiography were included in the study. Student t test, chi-square/fisher exact test have been used to find the significance of study parameters.Results: Out of total 111 patients with PAD included in the study, 98 patients were male. 61.1% of patients had co-existing significant CAD and significant PAD. Diabetes was a strong predictor of CAD (p=0.003) and smoking was strongly related to PAD (p=0.028). Elderly patients were associated with occurrence of significant CAD as well as PAD.  Conclusions: It can be concluded that there is a definite and significant correlation between PAD and CAD. The elderly population and those at increased risk for atherosclerotic vascular disease have higher liability of PAD; however, PAD is the condition that is mostly under diagnosed and under treated. The awareness about the co-existence of CAD and PAD, and implementation of co-diagnosis in general clinical practice has been poor.  

Genetic Interactions Effects of Cardiovascular Disorder Using Computational Models: A Review

2020 ◽  
Vol 9 (3) ◽  
pp. 177-191
Author(s):  
Sridharan Priya ◽  
Radha K. Manavalan
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Computational Models ◽  
Genetic Interaction ◽  
Association Studies ◽  
Genetic Interactions ◽  
Computational Techniques ◽  
Genome Wide Association Studies ◽  
Artery Disease

Background: The diseases in the heart and blood vessels such as heart attack, Coronary Artery Disease, Myocardial Infarction (MI), High Blood Pressure, and Obesity, are generally referred to as Cardiovascular Diseases (CVD). The risk factors of CVD include gender, age, cholesterol/ LDL, family history, hypertension, smoking, and genetic and environmental factors. Genome- Wide Association Studies (GWAS) focus on identifying the genetic interactions and genetic architectures of CVD. Objective: Genetic interactions or Epistasis infer the interactions between two or more genes where one gene masks the traits of another gene and increases the susceptibility of CVD. To identify the Epistasis relationship through biological or laboratory methods needs an enormous workforce and more cost. Hence, this paper presents the review of various statistical and Machine learning approaches so far proposed to detect genetic interaction effects for the identification of various Cardiovascular diseases such as Coronary Artery Disease (CAD), MI, Hypertension, HDL and Lipid phenotypes data, and Body Mass Index dataset. Conclusion: This study reveals that various computational models identified the candidate genes such as AGT, PAI-1, ACE, PTPN22, MTHR, FAM107B, ZNF107, PON1, PON2, GTF2E1, ADGRB3, and FTO, which play a major role in genetic interactions for the causes of CVDs. The benefits, limitations, and issues of the various computational techniques for the evolution of epistasis responsible for cardiovascular diseases are exhibited.

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