Prediction of Blood Pressure and Blood Pressure Change With a Genetic Risk Score.
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ABSTRACT:
SUBMITTER: Niiranen TJ
PROVIDER: S-EPMC8032027 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age2, sex and body mass index. Results were combined using an inverse-variance meta-analysis. The risk score was significantly associated with blood pressure in our combined sample (P=5.65 × 10-4 for systolic and P=1.65 × 10-3 for diastolic) but the magnitude of the effect sizes varied by degree of European, African and Native American admixture. Further studies among other Hispanic sub-populations are needed to elucidate the role of these 29 variants and identify additional genetic and environmental factors contributing to blood pressure variability in Hispanics.
| S-EPMC6456256 | biostudies-literature
Project description:We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (P=2.7×10-8, 9.8×10-8, and 6.4×10-6, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (P=1.4×10-3, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (P=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension.
| S-EPMC6443381 | biostudies-literature
Project description:BACKGROUND:To compare the reproducibility in total cholesterol (TC), systolic blood pressure (BP), and the resulting Systematic COronary Risk Evaluation (SCORE) obtained by an in-office cardio-preventive screening program (SP) and a subsequent program performed in a clinical trial examination center (EP). METHODS:A total of 307 individuals (60.3% female, mean age = 52.8 years) participated. According to TC and BP measurements at the SP and EP, three variables were created: the SCORESP = single BP reading at the SP, the SCOREEP/BP-first = first BP reading at the EP, and the SCOREEP/BP-mean = mean second/third BP reading at the EP. Differences in TC and BP were analyzed. Associations between age, sex and mean differences between the SCORESP and the SCOREEP/BP-first (M1) and the SCOREEP/BP-mean (M2) were analyzed using multivariable linear and quantile regression. RESULTS:TC and BP values from the SP were significantly higher than those from the EP. Among individuals with a decreased SCORE value at the EP (compared to the SP), younger age was associated with a higher improvement in risk estimation compared with older age. Female sex was associated with higher risk improvement in the SCORE between the SP and the EP compared with male sex. Associations between both demographics and M1 (M2) achieved statistical significance at the 75.0th (50th) percentile. CONCLUSIONS:The reproducibility of results in cardiovascular risk prediction seems to be influenced by the accuracy of BP measurement. It seems that younger individuals and females are more likely to benefit from accuracy compared with older individuals and males.
| S-EPMC5935918 | biostudies-literature
Project description:Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32,669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance-weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10(-62)). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07-1.46; P=0.006) and 1.23 (1.05-1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01-1.53; P=0.04) and 1.35 (1.09-1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08-1.40; P=2 × 10(-6)) and 1.26 (1.11-1.44; P=5 × 10(-4)), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.
| S-EPMC3648219 | biostudies-literature
Project description:Background and objectivesWhether using both traditional risk factors and genetic variants for stroke as opposed to using either of the 2 alone improves the prediction of stroke risk remains unclear. The purpose of this study was to compare the predictability of stroke risk between models using traditional risk score (TRS) and genetic risk score (GRS).MethodsWe used a case-cohort study from the Korean Cancer Prevention Study-II (KCPS-II) Biobank (n=156,701). We genotyped 72 single nucleotide polymorphisms (SNPs) identified in genome-wide association study (GWAS) on the KCPS-II sub-cohort members and stroke cases. We calculated GRS by summing the number of risk alleles. Prediction models with or without GRS were evaluated in terms of the area under the receiver operating characteristic curve (AUROC).ResultsSixteen out of 72 SNPs identified in GWAS showed significant associations with stroke, with an odds ratio greater than 2.0. For participants aged <40 years, AUROCs for incident stroke were 0.58, 0.65, and 0.67 in models using modifiable TRS only, GRS only, and TRS plus GRS, respectively, showing that GRS only model had better prediction than TRS only. For participants aged ≥40 years, however, TRS only model had better prediction than GRS only model. Favorable levels of traditional risk were associated with significantly lower stroke risks within each genetic risk category.ConclusionsTRS and GRS were both independently associated with stroke risk. Using genetic variants in addition to traditional risk factors may be the most accurate way of predicting stroke risk, particularly in relatively younger individuals.
| S-EPMC6072664 | biostudies-literature
Project description:Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS) combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS) and a weighted (wGRS) approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7) versus 12.09 (SD 1.8), p?=?4.577×10(-40). The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57), p?=?2.010×10(-65). To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC). The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p?=?2.13×10(-8)). Additionally, the AUC for HLA-C alone (rs10484554) was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p?=?0.18), highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p?=?4.91×10(-6)) and family history (p?=?0.020). Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.
| S-EPMC3084857 | biostudies-literature
Project description:Effective prevention of Alzheimer's disease (AD) requires the development of risk prediction tools permitting preclinical intervention. We constructed a genetic risk score (GRS) comprising common genetic variants associated with AD, evaluated its association with incident AD and assessed its capacity to improve risk prediction over traditional models based on age, sex, education, and APOEɛ4. In eight prospective cohorts included in the International Genomics of Alzheimer's Project (IGAP), we derived weighted sum of risk alleles from the 19 top SNPs reported by the IGAP GWAS in participants aged 65 and older without prevalent dementia. Hazard ratios (HR) of incident AD were estimated in Cox models. Improvement in risk prediction was measured by the difference in C-index (Δ-C), the integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI>0). Overall, 19,687 participants at risk were included, of whom 2,782 developed AD. The GRS was associated with a 17% increase in AD risk (pooled HR = 1.17; 95% CI = [1.13-1.21] per standard deviation increase in GRS; p-value = 2.86×10-16). This association was stronger among persons with at least one APOEɛ4 allele (HRGRS = 1.24; 95% CI = [1.15-1.34]) than in others (HRGRS = 1.13; 95% CI = [1.08-1.18]; pinteraction = 3.45×10-2). Risk prediction after seven years of follow-up showed a small improvement when adding the GRS to age, sex, APOEɛ4, and education (Δ-Cindex = 0.0043 [0.0019-0.0067]). Similar patterns were observed for IDI and NRI>0. In conclusion, a risk score incorporating common genetic variation outside the APOEɛ4 locus improved AD risk prediction and may facilitate risk stratification for prevention trials.
| S-EPMC5036102 | biostudies-literature
Project description:BackgroundDisease-related single nucleotide polymorphisms (SNPs) based genetic risk score (GRS) has been proven to provide independent inherited risk other than family history in multiple cancer types.AimTo evaluate the potential of GRS in the prediction of pancreatic cancer risk.MethodsIn this case-control study (254 cases and 1200 controls), we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma (PDAC) risk in the Chinese population. The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject (personal genotyping information of the SNPs) and was weighted by external odd ratios (ORs).ResultsGRS was significantly different in cases and controls (1.96 ± 3.84 in PDACs vs 1.09 ± 0.94 in controls, P < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, P < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, P = 0.015) after adjusting for age and sex. Further analysis revealed an association of increased risk for PDAC with higher GRS. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to have PDAC (OR: 1.99, 95%CI: 1.30-3.04, P = 0.002). Participants with intermediate GRS (1.0-1.9) were 39% more likely to have PDAC (OR: 1.39, 95%CI: 1.03-1.84, P = 0.031). A positive trend was observed (P trend = 0.0006).ConclusionGRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.
| S-EPMC7304113 | biostudies-literature
Project description:ImportanceLong-term cumulative systolic blood pressure (SBP) is significantly associated with increased rates of atherosclerotic cardiovascular disease (ASCVD) development independent of single SBP levels. However, published ASCVD risk prediction algorithms only include currently measured SBP.ObjectiveTo determine whether including long-term (5- and 10-year) cumulative SBP in risk equations improves the predictive ability compared with single SBP measurements.Design, setting, and participantsAdults aged 45 to 65 years at the time of risk estimation with at least 20 years of follow-up (5 and 10 years prior to risk estimation and 10 years of event follow-up). The Lifetime Risk Pooling Project included data from the following cohorts: Coronary Artery Risk Development in Young Adults Study, Atherosclerosis Risk in Communities Study, and Framingham Heart Study (both the original and offspring).ExposuresTen-year ASCVD risk, calculated using the approach of the 2013 American College of Cardiology/American Heart Association 10-year ASCVD risk equations, first with current SBP and then substituting 5- and 10-year cumulative SBP levels.Main outcomes and measuresIncident ASCVD events that occurred over 10 years of follow-up, compared with the predicted risks, using the C statistic, net reclassification index at event rate, and the integrated discrimination index.ResultsThis study included 11 767 participants with a mean (SD) age of 59.1 (4.7) years at risk estimation. A total of 6873 participants (58%) were women, and 1499 (13%) were African American. In the 10 years of follow-up from risk estimation, 1887 participants (16%) had an ASCVD event. There were no significant improvements in the C statistic when including 5- or 10-year cumulative SBP. However, the addition of cumulative SBP resulted in significant improvements in the net reclassification index at event rate (10-year net reclassification index for men, 0.04 [95% CI, 0.02-0.06]; 10-year net reclassification index for women, 0.03 [95% CI, 0.01-0.06]) and the relative integrated discrimination index (10-year relative integrated discrimination index for men, 0.12; 10-year relative integrated discrimination index for women, 0.10).Conclusions and relevanceUsing long-term measures of cumulative blood pressure, instead of single measurements, can modestly improve the ability of cardiovascular disease risk prediction models to correctly classify individuals in terms of their risk for cardiovascular disease.
| S-EPMC6583053 | biostudies-literature
Project description:Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke.Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5% (95% confidence interval, 51.3-53.7) for men and 39.9% (95% confidence interval, 38.7-41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22% to 41%, compared with individuals who had or developed hypertension by 55 years of age, 42% to 69%, suggesting a dose-response effect for the length of time at high BP levels.Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD.
| S-EPMC3310202 | biostudies-literature