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Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.

ABSTRACT: The concept of breeding values, an individual's phenotypic deviation from the population mean as a result of the sum of the average effects of the genes they carry, is of great importance in livestock, aquaculture, and cash crop industries where emphasis is placed on an individual's potential to pass desirable phenotypes on to the next generation. As breeding or genetic values (as referred to here) cannot be measured directly, estimated genetic values (EGVs) are based on an individual's own phenotype, phenotype information from relatives, and, increasingly, genetic data. Because EGVs represent additive genetic variation, calculating EGVs in an extended human pedigree is expected to provide a more refined phenotype for genetic analyses. To test the utility of EGVs in genome-wide association, EGVs were calculated for 847 members of 20 extended Mexican American families based on 100 replicates of simulated systolic blood pressure. Calculations were performed in GAUSS to solve a variation on the standard Best Linear Unbiased Predictor (BLUP) mixed model equation with age, sex, and the first 3 principal components of sample-wide genetic variability as fixed effects and the EGV as a random effect distributed around the relationship matrix. Three methods of calculating kinship were considered: expected kinship from pedigree relationships, empirical kinship from common variants, and empirical kinship from both rare and common variants. Genome-wide association analysis was conducted on simulated phenotypes and EGVs using the additive measured genotype approach in the SOLAR software package. The EGV-based approach showed only minimal improvement in power to detect causative loci.

SUBMITTER: Quillen EE

PROVIDER: S-EPMC4143678 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.

Quillen Ellen E EE Voruganti V Saroja VS Chittoor Geetha G Rubicz Rohina R Peralta Juan M JM Almeida Marcio Aa MA Kent Jack W JW Diego Vincent P VP Dyer Thomas D TD Comuzzie Anthony G AG Göring Harald Hh HH Duggirala Ravindranath R Almasy Laura L Blangero John J

BMC proceedings 20140617 Suppl 1 Genetic Analysis Workshop 18Vanessa Olmo

The concept of breeding values, an individual's phenotypic deviation from the population mean as a result of the sum of the average effects of the genes they carry, is of great importance in livestock, aquaculture, and cash crop industries where emphasis is placed on an individual's potential to pass desirable phenotypes on to the next generation. As breeding or genetic values (as referred to here) cannot be measured directly, estimated genetic values (EGVs) are based on an individual's own phen ...[more]

PMID: 25519398

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Project description:Rationale and objectiveAlthough low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality.Study designLongitudinal analysis of clinical trial participants.Settings and participants7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors.PredictorseGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits.OutcomesThe SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up.Analytical approachCox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18.ResultsMean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up.LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded.ConclusionsIn trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Project description:ImportanceExtremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events (ie, the diastolic J-shape phenomenon); however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure.ObjectivesTo evaluate whether there is a diastolic J-shape phenomenon for patients with an treated systolic blood pressure of less than 130 mm Hg and to explore the safe and optimal diastolic blood pressure ranges for this patient population.Design, setting, and participantsThis cohort study analyzed outcome data of patients at high cardiovascular risk who were randomized to intensive or standard blood pressure control and achieved treated systolic blood pressure of less than 130 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. Data were collected from October 2010 to August 2015 (SPRINT) and from September 1999 to June 2009 (ACCORD-BP). Data were analyzed from January to May 2020.ExposureTreated diastolic blood pressure, divided in intervals of less than 60, 60 to less than 70, 70 to less than 80, and 80 mm Hg and greater.Main outcomes and measuresThe primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. A composite cardiovascular outcome, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was among the key secondary outcomes.ResultsA total of 7515 patients (mean [SD] age, 65.6 [8.7] years; 4553 [60.6%] men) were included in this analysis. The nominally lowest risk was observed at a diastolic blood pressure between 70 and 80 mm Hg for the primary outcome, the composite cardiovascular outcome, nonfatal myocardial infarction, and cardiovascular death. A mean diastolic blood pressure of less than 60 mm Hg was associated with significantly increased risk of the primary outcome (hazard ratio [HR], 1.46; 95% CI, 1.13-1.90; P = .004), the composite cardiovascular outcome (HR, 1.74; 95% CI, 1.26-2.41; P = .001), nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.15-2.59; P = .008), and nonfatal stroke (HR, 2.67; 95% CI, 1.26-5.63; P = .01).Conclusions and relevanceThis cohort study found that lowering diastolic blood pressure to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated systolic blood pressure less than 130 mm Hg. The finding that a diastolic blood pressure value between 70 and 80 mm Hg was an optimum target for this patient population merits further study.

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Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.

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Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.

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