Multi-Center Genetic Study of Hypertension

Boerwinkle, Eric; Brown, C. Andrew; Carrejo, Maurita; Ferrell, Robert E.; Hanis, Craig L.; Hutchinson, Richard G.; Kardia, Sharon L.R.; Sing, Charles F.; Turner, Stephen T.; Weder, Alan B.; Chakravarti, Aravinda; Cooper, Richard S.; Jacob, Howard J.; Schork, Nicholas J.; Hunt, Steven C.; Arnett, Donna K.; Borecki, Ingrid B.; Eckfeldt, John H.; Ellison, R. Curtis; Gu, C. Charles; Heiss, Gerardo; Leppert, M.; Oberman, Albert; Province, Michael A.; Rao, D. C.; Cox, David; Curb, J. David; Chen, Ida; Grove, John S.; Quertermous, Thomas; Ranade, Koustubh; Risch, Neil; Rodríguez, Beatriz L.; Mockrin, Stephen; Old, Susan E.; Savage, Peter J.

doi:10.1161/hy1201.100415

Cited by 161 publications

(61 citation statements)

References 15 publications

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“…The study design and recruitment have been previously described. 14 The four networks used common definitions and standardised measurement protocols to facilitate pooling of results. 15 This current study included all women from all networks who reported at least one pregnancy lasting more than 6 months, and who had an echocardiogram.…”

Section: Methods Participantsmentioning

confidence: 99%

Left ventricular hypertrophy after hypertensive pregnancy disorders

Scantlebury

Kane

Wiste

et al. 2015

Heart

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Objective Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesized that women with a history of hypertensive pregnancy would have altered left ventricular (LV) geometry and function when compared to women with only normotensive pregnancies. Methods In this cohort study, we analyzed echocardiograms of 2637 women who participated in the Family Blood Pressure Program (FBPP). We compared LV mass and function in women with hypertensive pregnancy compared to those with normotensive pregnancies. Results Women were evaluated at a mean age of 56 years: 427 (16%) had at least one hypertensive pregnancy; 2210 (84%) had normotensive pregnancies. Compared to women with normotensive pregnancies, women with hypertensive pregnancy had a greater risk of LVH (OR: 1.42, 95% CI 1.01-1.99, p=0.05), after adjusting for age, race, research network of the FBPP, education, parity, BMI, hypertension and diabetes. When duration of hypertension was taken into account, this relationship was no longer significant (OR: 1.19, CI 0.08-1.78 p=0.38). Women with hypertensive pregnancies also had greater left atrial size and lower mitral E/A ratio after adjusting for demographic variables. The prevalence of systolic dysfunction was similar between the groups. Conclusions A history of hypertensive pregnancy is associated with LVH after adjusting for risk factors; this might be explained by longer duration of hypertension. This finding supports current guidelines recommending surveillance of women following a hypertensive pregnancy, and sets the stage for longitudinal echocardiographic studies to further elucidate progression of LV geometry and function after pregnancy.

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Section: Methods Participantsmentioning

confidence: 99%

Left ventricular hypertrophy after hypertensive pregnancy disorders

Scantlebury

Kane

Wiste

et al. 2015

Heart

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“…The longitudinal Genetic Epidemiology Network of Arteriopathy (GENOA) Study is one of four networks in the NHLBI Family-Blood Pressure Program and aims to elucidate the genetics of target organ complications of hypertension 21 . GENOA recruited European and African American sibships with at least 2 individuals with clinically diagnosed essential hypertension before age 60 years.…”

Section: Methodsmentioning

confidence: 99%

“…To maximize our sample size we conducted a multicenter transethnic association study in large population samples from four studies currently ongoing across the US: the Framingham Heart Study (FHS), the Coronary Artery Risk Development in Young Adults (CARDIA) 17 , the Multi-Ethnic Study of Atherosclerosis (MESA) 18, 19 and the Genetic Epidemiology Network of Arteriopathy (GENOA) 20, 21 .…”

Section: Introductionmentioning

confidence: 99%

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis

Dauriz

Porneala

Guo

et al. 2015

Circ Cardiovasc Genet

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Background Type 2 diabetes (T2D) and cardiovascular disease (CVD) share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results In a cross-sectional analysis including up to 9,210 European Americans, 3,773 African Americans, 1,446 Hispanic Americans and 773 Chinese Americans without known CVD and enrolled in the FHS, CARDIA, MESA and GENOA studies, we tested a 62 T2D-loci genetic risk score (GRS62) for association with measures of SCA, including coronary artery (CACS) or abdominal aortic calcium score, common (CCA-IMT) and internal carotid artery intima-media thickness, and ankle-brachial index (ABI). We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors adjusted model (significance = p<0.01 = 0.05/5, number of traits analyzed). An inverse association with CACS in MESA Europeans (fully-adjusted p=0.004) and with CCA-IMT in FHS (p=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance sub-GRS in FHS and CARDIA. Conclusions SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and CVD risk loci.

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“…SAPPHIRe recruited Chinese (CHI)and Japanese (JAP)sibpairs highly concordant or discordant for hypertension. More details on the participants are published elsewhere[24]. All FBPP studies were approved by their institutional review committees and all included participants provided informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…We fit a highly flexible generalized variance components model [23], which allowed both the heritability and the correlations among relatives to depend on age [23], in each of nine population groups from the Family Blood Pressure Program (FBPP) [24]. These nine groups represented3,600 African Americans (AAs), 1,283 Asians, 3,218 European Americans (EAs), and 2,026 Mexican Americans (MAs)[24]. We subsequently performed overall (across all races) and race-specific meta-analyses of these genome-widelinkage analysesto capitalize on the sharing of lipid loci across populations[3].…”

Section: Introductionmentioning

confidence: 99%

Linkage analysis incorporating gene–age interactions identifies seven novel lipid loci: The Family Blood Pressure Program

et al. 2014

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OBJECTIVE To detect novel loci with age-dependent effects on fasting (≥8 hours) levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides using3,600 African Americans, 1,283 Asians, 3,218 European Americans, and 2,026 Mexican Americans from the Family Blood Pressure Program (FBPP). METHODS Within each subgroup (defined by network, race, and sex), we employedstepwise linear regression (retention p≤0.05) to adjust lipid levels for age, age-squared, age-cubed,body-mass-index, current smoking status, current drinking status, field center, estrogen therapy (females only), as well asantidiabetic, antihypertensive, and antilipidemic medication use. For each trait, we pooled the standardized male and female residuals within each network and race and fit a generalized variance components model that incorporated gene-age interactions. We conducted FBPP-wide and race-specific meta-analyses by combining the p-values of each linkage marker across subgroups usinga modifiedFisher's method. RESULTS We identified seven novel loci with age-dependent effects; four total cholesterol loci from the meta-analysis of Mexican Americans (on chromosomes 2q24.1, 4q21.21, 8q22.2, and 12p11.23) and three high-density lipoprotein loci from the meta-analysis of all FBPP subgroups (on chromosomes 1p12, 14q11.2, and 21q21.1). These loci lacked significant genome-wide linkage or association evidence in the literature and hadlogarithm of odds (LOD) score ≥ 3 in the meta-analysis with LOD≥1 in at least two network and race subgroups (exclusively of non-European descent). CONCLUSION Incorporating gene-age interactions into the analysis of lipids using multi-ethnic cohorts can enhance gene discovery. These interaction loci can guide the selection of familiesfor sequencingstudies of lipid-associated variants.

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Multi-Center Genetic Study of Hypertension

Cited by 161 publications

References 15 publications

Left ventricular hypertrophy after hypertensive pregnancy disorders

Left ventricular hypertrophy after hypertensive pregnancy disorders

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis

Linkage analysis incorporating gene–age interactions identifies seven novel lipid loci: The Family Blood Pressure Program

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