Donna K Arnett

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Publications (485)2670.52 Total impact

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    ABSTRACT: Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2,097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed effects regression models were used to test the association of methylation beta value with concurrent BMI and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole blood DNA from 2,377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the GOLDN Study was followed by testing using adipose tissue DNA from 648 women in the MuTHER cohort. Seventy-six (76) BMI-related probes, 164 WC-related probes, and 8 BMI change-related probes passed the threshold for significance in ARIC (p<1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A, and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen (16) of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling, and other diverse pathways, including LGALS3BP, KDM2B, PBX1, and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity, and analytic approaches. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Molecular Genetics 05/2015; DOI:10.1093/hmg/ddv161 · 6.68 Impact Factor
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    ABSTRACT: The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care. © 2015 American Heart Association, Inc.
    Circulation 04/2015; 131(19). DOI:10.1161/CIR.0000000000000211 · 14.95 Impact Factor
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    ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (encoded by PCSK9) plays a well-known role in the regulation of low-density lipoprotein (LDL) receptors, and an inhibitor of this enzyme is a promising new therapeutic for hyperlipidemia. Recently, animal and human studies also implicate PCSK9 genetic variation in the regulation of blood pressure. The goal of this study was to examine if common and rare polymorphisms in PCSK9 are associated with blood pressure in an African-American population at high risk for cardiovascular disease. Using genomic data assayed on the Affymetrix 6.0 array (n = 1199) and the Illumina HumanExome Beadchip (n = 1966) from the Hypertension Genetic Epidemiology Network (HyperGEN), we tested the association of PCSK9 polymorphisms with blood pressure. We used linear mixed models and the sequence kernel association test (SKAT) to assess the association of 31 common and 19 rare variants with blood pressure. The models were adjusted for age, sex, center, smoking status, principal components for ancestry and diabetes as fixed effects and family as a random effect. The results showed a marginally significant effect of two genome-wide association study (GWAS) single-nucleotide polymorphisms (SNPs) (rs12048828: β = 1.8, P = 0.05 and rs9730100: β = 1.0, P = 0.05) with diastolic blood pressure (DBP); however these results were not significant after correction for multiple testing. Rare variants were cumulatively associated with DBP (P = 0.04), an effect that was strengthened by restriction to non-synonymous or stop-gain SNPs (P = 0.02). While gene-based results for DBP did not replicate (P = 0.36), we found an association with SBP (P = 0.04) in the Reasons for Geographic And Racial Differences in Stroke study (REGARDS). The findings here suggest rare variants in PCSK9 may influence blood pressure among African Americans, laying the ground work for further validation studies.
    Frontiers in Genetics 04/2015; 6:136. DOI:10.3389/fgene.2015.00136
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    ABSTRACT: Cardiovascular diseases are among the most significant health problems in the United States today, with their major risk factor, hypertension, disproportionately affecting African Americans (AAs). Although GWAS have identified dozens of common variants associated with blood pressure (BP) and hypertension in European Americans, these variants collectively explain <2.5% of BP variance, and most of the genetic variants remain yet to be identified. Here, we report the results from rare-variant analysis of systolic BP using 94,595 rare and low-frequency variants (minor allele frequency, MAF, <5%) from the Illumina exome array genotyped in 2,045 HyperGEN AAs. In addition to single-variant analysis, 4 gene-level association tests were used for analysis: burden and family-based SKAT tests using MAF cutoffs of 1 and 5%. The gene-based methods often provided lower p values than the single-variant approach. Some consistency was observed across these 4 gene-based analysis options. While neither the gene-based analyses nor the single-variant analysis produced genome-wide significant results, the top signals, which had supporting evidence from multiple gene-based methods, were of borderline significance. Though additional molecular validations are required, 6 of the 16 most promising genes are biologically plausible with physiological connections to BP regulation. © 2015 S. Karger AG, Basel.
    Human Heredity 03/2015; 79(1):20-27. DOI:10.1159/000375373 · 1.64 Impact Factor
  • Donna K Arnett
    Circulation Cardiovascular Quality and Outcomes 02/2015; 8(2_suppl_1). DOI:10.1161/CIRCOUTCOMES.115.001757 · 5.66 Impact Factor
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    ABSTRACT: Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. The effects of Apolipoprotein E (Apo E) polymorphism on MetS are not well established. We conducted a cross-sectional study consisting of 1,551 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. MetS was defined according to the AHA-NHLBI-IDF-WHO Harmonized Criteria. We used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis. Our study population had a mean age (SD) of 56.5 (11.0) years and 49.7% had MetS. There was no association between the Apo E genotypes and MetS. The multivariable adjusted ORs (95% CI) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62-1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47), and 1.87 (0.91-3.85) for the Ɛ3/Ɛ3, Ɛ2/Ɛ2, Ɛ2/Ɛ3, Ɛ2/Ɛ4, Ɛ3/Ɛ4, and Ɛ4/Ɛ4 genotypes, respectively. In a secondary analysis, Ɛ2/Ɛ3 genotype was associated with 41% lower prevalence odds of low HDL [multivariable adjusted ORs (95% CI) = 0.59 (0.36-0.95)] compared to Ɛ3/Ɛ3 genotype. Our findings do not support an association between Apo E polymorphism and MetS in a multi-center population based study of predominantly white US men and women. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 02/2015; DOI:10.1002/dmrr.2638 · 3.59 Impact Factor
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    ABSTRACT: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). We conducted meta-analyses (N to 11668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein) and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma vs. erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary ALA and linoleic acid for DHA and DPA. Our findings reinforce earlier reports that genetically-based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Molecular Nutrition & Food Research 01/2015; DOI:10.1002/mnfr.201400734 · 4.91 Impact Factor
  • Donna K Arnett
    Journal of the American College of Cardiology 01/2015; 65(1):52-4. DOI:10.1016/j.jacc.2014.10.023 · 15.34 Impact Factor
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    ABSTRACT: BACKGROUND: Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health. OBJECTIVE: The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers. DESIGN: We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts. RESULTS: Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (beta = 0.0035, P = 4.90 x 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (beta = 0.0053, P = 1.05 x 10(-6)) and Chinese Americans (beta = 0.0028, P = 0.002) but not African Americans (beta = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: beta = 0.0118, P = 4.05 x 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (beta-coefficient reduced by 86%), with similar reductions in Hispanic Americans and Chinese Americans. CONCLUSIONS: Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.
    American Journal of Clinical Nutrition 01/2015; 101(2-2):398-406. DOI:10.3945/ajcn.114.094557 · 6.92 Impact Factor
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    ABSTRACT: -Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African-Americans. -The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides. The analysis was performed in 1,905 unrelated African-American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program. Regions showing admixture evidence were followed-up with family-based association analysis in 3,556 African-American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body-mass-index, and genome-wide mean ancestry to minimize the confounding due to population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (LDL-C), 8 (HDL-C), 14 (triglycerides) and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52,939 SNPs were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with HDL-C (2 SNPs), LDL-C (4 SNPs) and triglycerides (5 SNPs). The family data was used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions including genes with known associations for cardiovascular disease. -This study identified regions on chromosomes 7, 8, 14 and 19 and 11 SNPs from the fine-mapping analysis that were associated with HDL-C, LDL-C and triglycerides for further studies of cardiovascular disease in African-Americans.
    Circulation Cardiovascular Genetics 12/2014; 8(1). DOI:10.1161/CIRCGENETICS.114.000481 · 6.73 Impact Factor
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    ABSTRACT: Carotid intima-media thickness (cIMT) is a subclinical measure of atherosclerosis with mounting evidence that higher cIMT confers an increased risk of cardiovascular disease. The ryanodine receptor 3 gene (RYR3) has previously been linked to increased cIMT; however, the causal variants have not yet been localized. Therefore, we sequenced 339 480 bp encompassing 104 exons and 2 kb flanking region of the RYR3 gene in 96 HIV-positive white men from the extremes of the distribution of common cIMT from the Fat Redistribution and Metabolic Changes in HIV infection study (FRAM). We identified 2710 confirmed variants (2414 single-nucleotide polymorphisms (SNPs) and 296 insertion/deletions (indels)), with a mean count of 736 SNPs (ranging from 528 to 1032) and 170 indels (ranging from 128 to 214) distributed in each individual. There were 39 variants in the exons and 15 of these were non-synonymous, of which with only 4 were common variants and the remaining 11 were rare variants, one was a novel SNP. We confirmed that the common variant rs2229116 was significantly associated with cIMT in this design (P<7.9 × 10(-9)), and observed seven other significantly associated SNPs (P<10(-8)). These variants including the private non-synonymous SNPs need to be followed up in a larger sample size and also tested with clinical atherosclerotic outcomes.Journal of Human Genetics advance online publication, 11 December 2014; doi:10.1038/jhg.2014.104.
    Journal of Human Genetics 12/2014; 60(2). DOI:10.1038/jhg.2014.104 · 2.53 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 12/2014; DOI:10.1016/j.ajhg.2014.11.011 · 10.99 Impact Factor
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    ABSTRACT: Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (> 50%) and were located in the promoter region, Group 2 exhibited hypomethylation (< 50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (> 50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r = -0.66, P = 0.004). APOE methylation was significantly associated with age (minimum P = 2.06E-08) and plasma total cholesterol (minimum P = 3.53E-03). Finally, APOE methylation patterns differed across APOE ε variants (minimum P = 3.51E-05) and the promoter variant rs405509 (minimum P = 0.01), which further showed a significant interaction with age (P = 0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Aging cell 12/2014; 14(1). DOI:10.1111/acel.12293 · 5.94 Impact Factor
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    ABSTRACT: Very long-chain saturated fatty acids (VLSFA) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFA may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFA is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFA by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, SPTLC3 (serine palmitoyl-transferase, long-chain base subunit 3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and CERS4 (ceramide synthase 4). The SPTLC3 variant at rs680379 was associated with higher 20:0 (arachidic acid, p = 5.81x10-13). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (p = 2.65x10-40) and in analyses that adjusted for 20:0, with lower levels of 22:0 (behenic acid, p = 4.22x10-26) and 24:0 (lignoceric acid, p = 3.20x10-21). These novel associations highlight the inter-relationship of circulating VLSFA and sphingolipid synthesis.
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    ABSTRACT: Background Diastolic wall strain (DWS), defined using posterior wall thickness (PWT) measurements from standard echocardiographic images (DWS = [PWT(systole)-PWT(diastole)]/PWT(systole)), has been proposed as a marker of left ventricular (LV) diastolic stiffness. However, the equation for DWS is closely related to systolic radial strain, and whether DWS is associated with abnormal cardiac mechanics (reduced systolic strains and diastolic tissue velocities) is unknown. We sought to determine the relationship between DWS and systolic and diastolic cardiac mechanics. Methods We calculated DWS and performed speckle-tracking analysis in a large population- and family-based study (Hypertension Genetic Epidemiology Network [HyperGEN]; N = 1907 after excluding patients with ejection fraction [EF] < 50% or posterior wall motion abnormalities). We measured global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively) and early diastolic (e’) tissue velocities, and we determined the independent association of DWS with cardiac mechanics using linear mixed effects models to account for relatedness among study participants. We also prospectively performed receiver-operating characteristic (ROC) analysis of DWS for the detection of abnormal cardiac mechanics in a separate, prospective validation study (N = 35). Results In HyperGEN (age 51 ± 14 years, 59% female, 45% African-American, 57% hypertensive), mean DWS was 0.38 ± 0.05. DWS decreased with increasing comorbidity burden (β-coefficient -0.013 [95% CI -0.015, -0.011]; P < 0.0001). DWS was independently associated with GLS, GCS, GRS, and e’ velocity (adjusted P < 0.05) but not LV chamber compliance (EDV20, P = 0.97). On prospective speckle-tracking analysis, DWS correlated well with GLS, GCS, and GRS (R = 0.61, 0.57, and 0.73, respectively; P < 0.001 for all comparisons). C-statistics for DWS as a diagnostic test for abnormal GLS, GCS, and GRS were: 0.78, 0.79, and 0.84, respectively. Conclusions DWS, a simple parameter than can be calculated from routine 2D echocardiography, is closely associated with systolic strain parameters and early diastolic (e’) tissue velocities but not LV chamber compliance.
    Cardiovascular Ultrasound 10/2014; 12(1):40. DOI:10.1186/1476-7120-12-40 · 1.28 Impact Factor
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    ABSTRACT: Cardiac hypertrophy is an independent risk factor for cardiovascular disease and heart failure. There is increasing evidence that microRNAs (miRNAs) play an important role in the regulation of messenger RNA (mRNA) and the pathogenesis of various cardiovascular diseases. However, the ability to comprehensively study cardiac hypertrophy on a gene regulatory level is impacted by the limited availability of human cardiomyocytes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer the opportunity for disease modeling. Here we utilize a previously established in vitro model of cardiac hypertrophy to interrogate the regulatory mechanism associated with the cardiac disease process. We perform miRNA sequencing and mRNA expression analysis on endothelin 1 (ET-1) stimulated hiPSC-CMs to describe associated RNA expression profiles. MicroRNA sequencing revealed over 250 known and 34 predicted novel miRNAs to be differentially expressed between ET-1 stimulated and unstimulated control hiPSC-CMs. Messenger RNA expression analysis identified 731 probe sets with significant differential expression. Computational target prediction on significant differentially expressed miRNAs and mRNAs identified nearly 2000 target pairs. A principal component analysis approach comparing the in vitro data with human myocardial biopsies detected overlapping expression changes between the in vitro samples and myocardial biopsies with Left Ventricular Hypertrophy. These results provide further insights into the complex RNA regulatory mechanism associated with cardiac hypertrophy.
    PLoS ONE 09/2014; 9(9):e108051. DOI:10.1371/journal.pone.0108051 · 3.53 Impact Factor
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    ABSTRACT: Previous studies have reported that risk of cardiovascular morbidity and mortality substantially increases in hypertensive patients, especially among those with inadequate blood pressure control. Two common antihypertensive drug classes including thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors affect different enzymes in the renin-angiotensin-aldosterone system (RAAS). In the RAAS, angiotensinogen is converted into angiotensin II which increases blood pressure through vasoconstriction. Using a case-only design with 3448 high-risk hypertensive individuals from the Genetics of Hypertension Associated Treatment (GenHAT) study, we examined whether seven single nucleotide polymorphisms (SNPs) in the angiotensinogen gene (AGT) interact with three classes of antihypertensive drugs including chlorthalidone (a thiazide diuretic), lisinopril (an ACE inhibitor), and amlodipine (a calcium channel blocker) to modify the risk of incident coronary heart disease (CHD) and heart failure (HF) among Caucasian and African American participants, separately. We found no gene by treatment interactions to be statistically significant after correction for multiple testing. However, some suggestive results were found. African American participants with the minor allele of rs11122576 had over two-fold higher risk of CHD when using chlorthalidone compared to using amlodipine, or lisinopril compared to amlodipine (p = 0.006 and p = 0.01, respectively). Other marginal associations are also reported among both race groups. The findings reported here suggest that rs11122576 could contribute to future personalization of antihypertensive treatment among African Americans though more studies are needed.
    Frontiers in Pharmacology 09/2014; 5:210. DOI:10.3389/fphar.2014.00210
  • Circulation 09/2014; 130(18). DOI:10.1161/CIR.0000000000000128 · 14.95 Impact Factor
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    ABSTRACT: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716).
    BMC Genomics 09/2014; 15(1):781. DOI:10.1186/1471-2164-15-781 · 4.04 Impact Factor
  • Journal of the American College of Cardiology 09/2014; 64(17). DOI:10.1016/j.jacc.2014.07.012 · 15.34 Impact Factor

Publication Stats

13k Citations
2,670.52 Total Impact Points

Institutions

  • 2005–2015
    • University of Alabama at Birmingham
      • Department of Epidemiology
      Birmingham, Alabama, United States
    • University of Oslo
      • Department of Nutrition
      Kristiania (historical), Oslo, Norway
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2014
    • American Heart Association
      Dallas, Texas, United States
  • 1997–2014
    • University of Minnesota Duluth
      • • Laboratory Medicine and Pathology
      • • Department of Family Medicine and Community Health
      Duluth, Minnesota, United States
  • 2006–2013
    • University of Alabama
      Tuscaloosa, Alabama, United States
    • University of Utah
      • Division of Cardiovascular Genetics
      Salt Lake City, UT, United States
  • 2012
    • United States Department of Agriculture
      Washington, Washington, D.C., United States
  • 2011
    • Oregon Health and Science University
      • Bone and Mineral Unit
      Portland, OR, United States
  • 2005–2010
    • Weill Cornell Medical College
      • Department of Medicine
      New York, New York, United States
  • 2000–2010
    • Washington University in St. Louis
      • • Division of Biostatistics
      • • Department of Genetics
      San Luis, Missouri, United States
  • 2009
    • Universiteit Utrecht
      • Division of Pharmacoepidemiology and Pharmacotherapy
      Utrecht, Provincie Utrecht, Netherlands
    • University of Minnesota Twin Cities
      • Department of Laboratory Medicine and Pathology
      Minneapolis, MN, United States
  • 2004–2007
    • Cornell University
      Итак, New York, United States
  • 2003–2005
    • Boston University
      • Section of Preventive Medicine and Epidemiology
      Boston, MA, United States
  • 2001–2005
    • New York Presbyterian Hospital
      • Department of Pain Medicine
      New York City, New York, United States
  • 2002
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1999
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Pennsylvania State University
      University Park, Maryland, United States
  • 1992–1996
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      North Carolina, United States
  • 1991
    • University of South Florida
      • Department of Cardiology
      Tampa, FL, United States