Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk fact... more Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 ...
To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on program... more To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β = -1.1% per quartile; 95% CI: -2.0, -0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.
Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of andro... more Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FVIIc) and fibrinogen levels, which are regulated by TFPI and are independent risk predictors for CAD. We conducted the analysis in both Chinese adult (N = 309) and neonatal cohorts (N = 447). The genotypes of the rs6903956 single nucleotide polymorphism (SNP) were determined by the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). FVIIc and fibrinogen level were measured from citrated plasma. The association between rs6903956 and coagulation factors was tested by linear r...
Background and Purpose —One in 10 deaths in Australia is due to stroke. The predictors of ischemi... more Background and Purpose —One in 10 deaths in Australia is due to stroke. The predictors of ischemic stroke have not been well defined, although hypertension, atrial fibrillation, and previous stroke have been consistently reported. We report on 98 months’ follow-up in a prospective study of cardiovascular disease in the Australian elderly, the Dubbo Study. Methods —The cohort, first examined in 1988, was composed of 2805 men and women 60 years and older. The prediction of ischemic stroke by potential risk factors was examined in a Cox proportional hazards model, after linkage to hospital and death records. Results —Three hundred six men and women manifested an ischemic stroke event (ICD-9-CM 433 to 437), and 95 subjects suffered a fatal stroke event. In the multivariate model, the significant independent predictors of stroke were advancing age, female sex (48% lower risk), being married (30% lower risk), prior history of stroke (227% higher risk), use of antihypertensive drugs (37% h...
Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (m... more Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. Methods and Results— We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m 2 higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) hig...
1. Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular disease in the elderly. Am J Cardi... more 1. Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular disease in the elderly. Am J Cardiol 1989;63:12H–19H. 2. Aronow WS, Ahn C. Correlation of serum lipids with the presence or absence of coronary artery disease in 1,793 men and women aged 62 years. Am J Cardiol 1994;73:702–703. 3. Aronow WS, Ahn C. Risk factors for new coronary events in a large cohort of very elderly patients with and without coronary artery disease. Am J Cardiol 1996;77:864–866. 4. Miettinen TA, Pyorala K, Olsson AG, Musliner TA, Cook TJ, Faergeman O, Berg K, Pedersen T, Kjekshus J, for the Scandinavian Simvastatin Study Group. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris. Findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997;96:4211–4218. 5. Lewis SJ, Moye LA, Sacks FM, Johnstone DE, Timmis G, Mitchell J, Limacher M, Kell S, Glasser SP, Grant J, et al, for the CARE Investigators. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) Trial. Ann Intern Med 1998;129:681–689. 6. Hunt D, Young P, Simes J, Hague W, Mann S, Owensby D, Lane G, Tonkin A, for the LIPID Investigators. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID Trial. Ann Intern Med 2001;134:931–940. 7. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol 1987;60:1182. 8. Roberts WC. Sudden cardiac death: definitions and causes. Am J Cardiol 1986;57:1410–1413. 9. Joint National Committee. The Sixth Report of the Joint National Committee on the Detection Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413–2444. 10. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197.
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk fact... more Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 ...
To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on program... more To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β = -1.1% per quartile; 95% CI: -2.0, -0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.
Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of andro... more Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FVIIc) and fibrinogen levels, which are regulated by TFPI and are independent risk predictors for CAD. We conducted the analysis in both Chinese adult (N = 309) and neonatal cohorts (N = 447). The genotypes of the rs6903956 single nucleotide polymorphism (SNP) were determined by the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). FVIIc and fibrinogen level were measured from citrated plasma. The association between rs6903956 and coagulation factors was tested by linear r...
Background and Purpose —One in 10 deaths in Australia is due to stroke. The predictors of ischemi... more Background and Purpose —One in 10 deaths in Australia is due to stroke. The predictors of ischemic stroke have not been well defined, although hypertension, atrial fibrillation, and previous stroke have been consistently reported. We report on 98 months’ follow-up in a prospective study of cardiovascular disease in the Australian elderly, the Dubbo Study. Methods —The cohort, first examined in 1988, was composed of 2805 men and women 60 years and older. The prediction of ischemic stroke by potential risk factors was examined in a Cox proportional hazards model, after linkage to hospital and death records. Results —Three hundred six men and women manifested an ischemic stroke event (ICD-9-CM 433 to 437), and 95 subjects suffered a fatal stroke event. In the multivariate model, the significant independent predictors of stroke were advancing age, female sex (48% lower risk), being married (30% lower risk), prior history of stroke (227% higher risk), use of antihypertensive drugs (37% h...
Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (m... more Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. Methods and Results— We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m 2 higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) hig...
1. Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular disease in the elderly. Am J Cardi... more 1. Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular disease in the elderly. Am J Cardiol 1989;63:12H–19H. 2. Aronow WS, Ahn C. Correlation of serum lipids with the presence or absence of coronary artery disease in 1,793 men and women aged 62 years. Am J Cardiol 1994;73:702–703. 3. Aronow WS, Ahn C. Risk factors for new coronary events in a large cohort of very elderly patients with and without coronary artery disease. Am J Cardiol 1996;77:864–866. 4. Miettinen TA, Pyorala K, Olsson AG, Musliner TA, Cook TJ, Faergeman O, Berg K, Pedersen T, Kjekshus J, for the Scandinavian Simvastatin Study Group. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris. Findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997;96:4211–4218. 5. Lewis SJ, Moye LA, Sacks FM, Johnstone DE, Timmis G, Mitchell J, Limacher M, Kell S, Glasser SP, Grant J, et al, for the CARE Investigators. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) Trial. Ann Intern Med 1998;129:681–689. 6. Hunt D, Young P, Simes J, Hague W, Mann S, Owensby D, Lane G, Tonkin A, for the LIPID Investigators. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID Trial. Ann Intern Med 2001;134:931–940. 7. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol 1987;60:1182. 8. Roberts WC. Sudden cardiac death: definitions and causes. Am J Cardiol 1986;57:1410–1413. 9. Joint National Committee. The Sixth Report of the Joint National Committee on the Detection Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413–2444. 10. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197.
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