scholarly journals Clinical Evaluation of the Polygenetic Background of Blood Pressure in the Population-Based Setting

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 169-177
Author(s):  
Alice Giontella ◽  
Marketa Sjögren ◽  
Luca A. Lotta ◽  
John D. Overton ◽  
Aris Baras ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Events ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Total Mortality ◽  
Genome Wide Association Studies ◽  
Clinical Value ◽  
Bottom Quartile ◽  
Diet And Cancer

The clinical value of the polygenetic component of blood pressure (BP) is commonly questioned. We evaluated a genetic risk score for BP (BP-GRS 858 ), based on the most recently published genome-wide association studies variants that were significantly associated with either systolic BP or diastolic BP, for prediction of hypertension and cardiovascular end points. The genotyping was performed in 2 urban-based prospective cohorts: the Malmö Diet and Cancer (n=29 295) and the Malmö Preventive Project (n=9367) and a weighted BP-GRS 858 based on 858 SNPs was calculated. At baseline, we found a difference of 9.0 mm Hg (systolic BP) and 4.8 mm Hg (diastolic BP) between the top and the bottom quartile of BP-GRS 858 . In Malmö Preventive Project, the top versus bottom quartile of BP-GRS 858 was associated with a doubled risk of incident hypertension (odds ratio, 2.05 [95% CI, 1.75–2.39], P =1.4×10 −21 ), a risk higher than that of body mass index, as evaluated in quartiles. In Malmö Diet and Cancer, significant association was found between the age and sex-adjusted BP-GRS 858 and the incidence of total cardiovascular events, stroke, coronary artery disease, heart failure, atrial fibrillation, and total mortality. Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. BP-GRS 858 could contribute predictive information regarding future hypertension, with an effect size comparable to other well-known risk factors such as obesity, and predicts cardiovascular events. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS 858 might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.

scholarly journals Association of Established Blood Pressure Loci With 10‐Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Alaitz Poveda ◽  
Naeimeh Atabaki‐Pasdar ◽  
Shafqat Ahmad ◽  
Göran Hallmans ◽  
Frida Renström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Genetic Variants ◽  
Association Studies ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Swedish Population ◽  
Long Term Changes ◽  
Traditional Risk Factors

Background Genome‐wide association studies have identified >1000 genetic variants cross‐sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure‐associated variants with long‐term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population. Methods and Results We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRS SBP ): 554 variants; diastolic blood pressure GRS (GRS DBP ): 481 variants; mean arterial pressure GRS (GRS MAP ): 20 variants; pulse pressure GRS (GRS PP ): 478 variants; hypertension GRS (GRS HTN ): 22 variants; combined GRS (GRS com b ): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRS comb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10‒1.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99‒1.25) while controlling for traditional risk factors. The addition of GRS comb to a model containing traditional risk factors only marginally improved discrimination (Δarea under the ROC curve = 0.001–0.002). Conclusions GRSs based on discovered blood pressure‐associated variants are associated with long‐term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.

The Association Between Genetic Risk Factors and the Size of Intracranial Aneurysms at Time of Rupture

Neurosurgery ◽  
2013 ◽  
Vol 73 (4) ◽  
pp. 705-708 ◽  
Author(s):  
Rachel Kleinloog ◽  
Femke N.G. van 't Hof ◽  
Franciscus J. Wolters ◽  
Ingeborg Rasing ◽  
Irene C. van der Schaaf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Intracranial Aneurysms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genetic Risk Factors ◽  
Genome Wide Association Studies ◽  
Aneurysm Size ◽  
Genome Wide

Abstract BACKGROUND: Genetic risk factors for intracranial aneurysms may influence the size of aneurysms. OBJECTIVE: To assess the association between genetic risk factors and the size of aneurysms at the time of rupture. METHODS: Genotypes of 7 independent single-nucleotide polymorphisms (SNPs) of the 6 genetic risk loci identified in genome-wide association studies of patients with intracranial aneurysms were obtained from 700 Dutch patients with an aneurysmal subarachnoid hemorrhage (1997-2007) previously genotyped in the genome-wide association studies; 255 additional Dutch patients with an aneurysmal subarachnoid hemorrhage (2007-2011) were genotyped for these SNPs. Aneurysms were measured on computerized tomography angiography or digital subtraction angiography. The mean aneurysm size (with standard error) was compared between patients with and without a genetic risk factor by the use of linear regression. The association between SNPs and size was assessed for single SNPs and for the combined effect of SNPs by using a weighted genetic risk score. RESULTS: Single SNPs showed no association with aneurysm size, nor did the genetic risk score. CONCLUSION: The 6 genetic risk loci have no major influence on the size of aneurysms at the time of rupture. Because these risk loci explain no more than 5% of the genetic risk, other genetic factors for intracranial aneurysms may influence aneurysm size and thereby proneness to rupture.

scholarly journals The Clinical Utility of Genetic Risk Scores Following Myocardial Infarction

2021 ◽  
Author(s):  
◽  
Hadley Northcott
Keyword(s):  
Risk Factors ◽  
New Zealand ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Traditional Risk Factors ◽  
Cad Risk

<p>Current risk assessment for the development of coronary artery disease (CAD) in an individual relies on a combination of clinical characteristics. These well-established CAD risk factors include consideration of age, gender, hypertension, dyslipidemia, diabetes, smoking and obesity. However there are a proportion of patients that experience an acute coronary syndrome (ACS) event despite being deemed as low risk based on the current New Zealand risk model. These patients present with an absence of the traditional risk factors, or they fall below the age threshold where CAD screening is initiated.  The lack of association with disease development and presence of the traditional risk factors in these patients has led to the hypothesis that genetics play a significant role in the etiology of their disease. The conduction of family-based hereditary studies has supported the hypothesis that CAD risk is associated with genetic markers. A method of analyzing this genetic risk has been developed in the form of calculating a genetic risk score (GRS). The GRS is comprised of a panel of single nucleotide polymorphisms (SNPs) discovered through genome wide association studies in CAD patients. Currently, there is controversy in the clinical utility of different GRS calculation methods, and as yet, there has been no research conducted on the potential benefits of a GRS in a New Zealand setting.  Our study measured genetic risk through a weighted GRS calculated from a 27 SNP panel in 420 patients in a New Zealand based population. In looking at whether we could determine a difference in GRS values between premature (young) MI patients and older control patients, we found that the mean GRS was not significantly elevated in the premature MI cohort (p = 0.156). However, in assessing GRS differences between ethnicities and in relation to specific risk factors we saw that mean GRS was higher in patients with a family history of coronary disease (p = 0.003), in Māori patients (p = 0.013) and in patients with fewer than 2 traditional risk features (p = 0.001). GRS was not associated with individual traditional risk factors, including dyslipidaemia, hypertension, diabetes, obesity or gender. Our results showed that genetic risk for CAD is identifiable with this GRS, and indicates that further research into ethnic differences and identifying genetic risk in young CAD patients with low traditional risk would provide interesting insights.</p>

Abstract 238: Genetic Risk Score as a Predictor of Incident Hypertension and Blood Pressure Change Over Time

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Teemu Niiranen ◽  
Juhani Mäki ◽  
Aki S Havulinna ◽  
Veikko Salomaa ◽  
Antti Jula
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Prevalence Odds Ratio ◽  
Change Over Time ◽  
Incident Hypertension ◽  
Over Time

Little data exist regarding single nucleotide polymorphisms (SNPs) predicting blood pressure (BP) change over time. We genotyped 32 common SNPs in a nationwide cohort aged ≥30 years examined in years 2000 (n=5402) and 2011 (n=3373). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident hypertension and BP change over time. We created GRSs for systolic and diastolic BP by multiplying the risk allele count of each SNP by the effect size estimated in published genome-wide association studies. In linear and logistic regression models adjusted for traditional risk factors, 1-unit increases in GRSs were associated with higher systolic and diastolic BP values both at baseline (β±SE, 1.04±0.14 mmHg and 1.11±0.13 mmHg; P<0.0001 for both) and at reinvestigation (β±SE, 0.86±0.18 mmHg and 0.74±0.16 mm Hg; P<0.0001 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.12 [1.08-1.16] and 1.18 [1.11-1.26]; P<0.0001 for both). Among all participants who were normotensive at baseline and participated in the re-examination (n=2045), the GRSs were not independently associated with BP change over time (β±SE, 0.016±0.18 mmHg and 0.019±0.18 mmHg; P≥0.27 for both). However, in the top tertile of the GRS, the predicted increase in BP compared with the bottom tertile was 1.59±0.78 mmHg greater for systolic BP (P=0.04) and 0.79±0.49 mmHg greater for diastolic BP (P=0.11) and the odds ratio for incident hypertension was 30% higher (P=0.04). Our data show that GRSs are strongly associated with BP and prevalence of hypertension, but only weakly associated with BP increase and incidence of hypertension in a general adult population.

scholarly journals The Clinical Utility of Genetic Risk Scores Following Myocardial Infarction

2021 ◽  
Author(s):  
◽  
Hadley Northcott
Keyword(s):  
Risk Factors ◽  
New Zealand ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Traditional Risk Factors ◽  
Cad Risk

<p>Current risk assessment for the development of coronary artery disease (CAD) in an individual relies on a combination of clinical characteristics. These well-established CAD risk factors include consideration of age, gender, hypertension, dyslipidemia, diabetes, smoking and obesity. However there are a proportion of patients that experience an acute coronary syndrome (ACS) event despite being deemed as low risk based on the current New Zealand risk model. These patients present with an absence of the traditional risk factors, or they fall below the age threshold where CAD screening is initiated.  The lack of association with disease development and presence of the traditional risk factors in these patients has led to the hypothesis that genetics play a significant role in the etiology of their disease. The conduction of family-based hereditary studies has supported the hypothesis that CAD risk is associated with genetic markers. A method of analyzing this genetic risk has been developed in the form of calculating a genetic risk score (GRS). The GRS is comprised of a panel of single nucleotide polymorphisms (SNPs) discovered through genome wide association studies in CAD patients. Currently, there is controversy in the clinical utility of different GRS calculation methods, and as yet, there has been no research conducted on the potential benefits of a GRS in a New Zealand setting.  Our study measured genetic risk through a weighted GRS calculated from a 27 SNP panel in 420 patients in a New Zealand based population. In looking at whether we could determine a difference in GRS values between premature (young) MI patients and older control patients, we found that the mean GRS was not significantly elevated in the premature MI cohort (p = 0.156). However, in assessing GRS differences between ethnicities and in relation to specific risk factors we saw that mean GRS was higher in patients with a family history of coronary disease (p = 0.003), in Māori patients (p = 0.013) and in patients with fewer than 2 traditional risk features (p = 0.001). GRS was not associated with individual traditional risk factors, including dyslipidaemia, hypertension, diabetes, obesity or gender. Our results showed that genetic risk for CAD is identifiable with this GRS, and indicates that further research into ethnic differences and identifying genetic risk in young CAD patients with low traditional risk would provide interesting insights.</p>

Abstract P258: Traditional Risk Factors and a Genetic Risk Score Are Associated with Age of First Acute Coronary Syndrome

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Christopher Labos ◽  
Leo Rui Wang ◽  
Louise Pilote ◽  
Peter Bogaty ◽  
James M Brophy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Risk Score ◽  
Genetic Risk ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Traditional Risk Factors

Background: Early onset myocardial infarction (MI) is frequently attributed to genetic factors that may accelerate the atherosclerotic process. However, early MI may also occur due to a high burden of traditional risk factors. We sought to examine the association between traditional risk factors as well as a genetic risk score on the age of a first acute coronary syndrome (ACS). Methods and Results: We included 460 participants (mean age 59 +/- 12 years, 22.4% female) with a first ACS enrolled in the Recurrence and Inflammation in the Acute Coronary Syndromes (RISCA) cohort. Participants were genotyped for 30 single nucleotide polymorphisms identified from prior myocardial infarction genome-wide association studies to construct a multilocus genetic risk score (GRS). Linear regression models were fit to estimate the association between traditional risk factors (TRFs) and the GRS with age of first ACS. Several TRFs were significantly associated with earlier age of first ACS (all β coefficients in years; p<0.05 for all) : male sex [β=-6.9 (95%CI -9.7,-4.1)], current cigarette smoking [β=-8.1 (95% confidence interval [CI] -10.0, -6.1)], overweight (BMI>25) [β=-2.6 (95%CI -4.8, -0.3)] and obesity (BMI>30) [β=-5.24 (95%CI -7.9, -2.6)]. Use of hormone replacement therapy [β=-4.3 (95%CI -8.4, -0.3) ] and aspirin use were also associated with age of first ACS [β=3.7 (95%CI 0.3, 7.0)]. After multivariable adjustment for TRFs, a one standard deviation increment in the GRS was associated with a 1.0 (95%CI 0.1-2.0) year earlier age of first ACS. Conclusion: Among individuals with a first ACS, a GRS composed of 30 SNPs is associated with a younger age of presentation. Although common genetic predisposition modestly contributes to earlier ACS, a heavy burden of traditional risk factors is strongly associated with markedly earlier ACS.

Fibrinogen and Factor Vllag in Healthy Adolescents: The Floren-teen (Florence Teenager) Study

1996 ◽  
Vol 75 (05) ◽  
pp. 778-781 ◽  
Author(s):  
Domenico Prisco ◽  
Sandra Fedi ◽  
Tamara Brunelli ◽  
Anna Paola Cellai ◽  
Mohamed Isse Hagi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Healthy Subjects ◽  
Cardiovascular Events ◽  
Independent Risk Factor ◽  
Factor Vii ◽  
Coronary Heart Disease Prevention ◽  
Familial History ◽  
Clear Cut ◽  
Adolescent Population

SummaryAt least five studies based on more than twenty thousand healthy subjects indicated that fibrinogen is an independent risk factor for cardiovascular events; less clear-cut is the relation between factor VII and risk for arterial thrombotic disorders, which was demonstrated in two of the three studies investigating this association. However, no study has investigated the behaviour of fibrinogen and factor VII in an adolescent population. In a study of Preventive Medicine and Education Program, fibrinogen (clotting method) and factor Vllag (ELISA), in addition to other metabolic parameters, life-style and familial history, were investigated in 451 students (313 females and 138 males, age 15-17 years) from two high schools of Florence. Fibrinogen levels were significantly higher in women than in men, whereas factor Vllag levels did not significantly differ. Both fibrinogen and factor Vllag significantly correlated with total cholesterol (p <0.05) while only fibrinogen correlated with body mass index (p <0.01). Factor Vllag was significantly correlated with systolic blood pressure (p <0.001). This study provides information on coagulation risk factors in a population of adolescents which may be of importance in planning coronary heart disease prevention programs.

scholarly journals Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323906
Author(s):  
Jue-Sheng Ong ◽  
Jiyuan An ◽  
Xikun Han ◽  
Matthew H Law ◽  
Priyanka Nandakumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Association Studies ◽  
Barrett’S Oesophagus ◽  
Oesophageal Reflux ◽  
Oesophageal Adenocarcinoma ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Disease Heterogeneity ◽  
Barrett's Oesophagus

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.

Abstract 13798: Ablation of the Hypertension Candidate Gene ATP2B1 Results in Increased Blood Pressure and Cardiac Hypertrophic Remodeling

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sally K Hammad ◽  
Min Zi ◽  
Sukhpal Prehar ◽  
Robert Little ◽  
Ludwig Neyses ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Diastolic Pressure ◽  
Association Studies ◽  
Weight Ratio ◽  
Blood Pressure Regulation ◽  
Heart Weight ◽  
Genome Wide Association Studies ◽  
Pressure Regulation ◽  
The Impact

Introduction: Hypertension is a major risk factor for cardiac hypertrophy and heart failure. Genome wide association studies have recently identified single nucleotide polymorphisms in ATP2B1 , the gene encoding the calcium extrusion pump, plasma membrane calcium ATPase (PMCA1), as having a strong association with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: We aim to examine whether there is a functional link between PMCA1 and blood pressure regulation, and the development of hypertension. And to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1 we generated a global PMCA1 heterozygous knockout mouse (PMCA1 Ht ). PMCA1 Ht mice had 46% to 52% reduction in PMCA1 protein expression compared to the WT, in aorta, heart, kidney and brain. To study the mice under hypertensive stress conditions, 3 month old PMCA1 Ht and wild type (WT) mice were infused via minipump with angiotensin II (1mg/Kg/daily) or water as a control. Upon angiotensin treatment, PMCA1 Ht mice showed a significantly greater increase in systolic (62.24±3.05 mmHg) and diastolic pressure (52.68±4.67 mmHg), in comparison to the WT (33.37±2.91 mmHg and 23.94±4.56 mmHg, respectively), P<0.001, n=12. Moreover, PMCA1 Ht mice showed a significantly greater hypertrophic response as indicated by a greater heart weight to tibia length ratio, cardiomyocyte cell size (410±18.7 μm 2 ), compared to WT mice (340.4±9.8 μm 2 ), and increased expression of B-type natriuretic peptide (BNP), 2.36 ± 0.25 fold change, n =5-6, P< 0.01. Echocardiography showed no significant changes between PMCA1 Ht and WT mice, in heart rate, and in cardiac function, as indicated by fractional shortening and ejection fraction. In addition, PMCA1 Ht mice showed no sign of lung congestion as indicated by lung weight to body weight ratio. Conclusion: ATP2B1 deletion leads to increased blood pressure and cardiac hypertrophy. This provides functional evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

Sign in / Sign up

Export Citation Format

Share Document