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Framingham Center, United States

Goto A.,Diabetes Research Center | Chen B.H.,Blood Institutes Framingham Heart Study | Song Y.,Harvard University | Cauley J.,University of Pittsburgh | And 11 more authors.
Clinical Chemistry | Year: 2014

BACKGROUND: Circulating concentrations of sex hormone- binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood. METHODS: We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study- and ethnicity-specific associations of age, reproductive history, usage of exogenous estrogen, body mass index (BMI), and lifestyle factors such as physical activity, smoking, alcohol consumption, coffee intake, and dietary factors with SHBG concentrations. These estimates were pooled using random-effects models. We also examined potential nonlinear associations using spline analyses. RESULTS: There was no significant ethnic difference in the age-adjusted mean concentrations of SHBG. Age, exogenous estrogen use, physical activity, and regular coffee intake were positively associated with SHBG concentrations, whereas BMI was inversely associated with SHBG concentrations after adjustment for potential confounding factors. Similar patterns were observed among both ever users and never users of exogenous estrogen. The spline analysis indicated nonlinear relations of regular intake of coffee, age, and BMI with SHBG concentrations. Two or more cups/day of regular coffee consumption and age of 60 years or older were associated with higher SHBG concentrations; the inverse BMI-SHBG relation was especially strong among women whose BMI was below 30. CONCLUSIONS: In this large sample of postmenopausal women, age, exogenous estrogen use, physical activity, regular coffee intake, and BMI were significant correlates of SHBG concentrations, presenting potential targets for interventions. © 2013 American Association for Clinical Chemistry.

Lam C.S.P.,Blood Institutes Framingham Heart Study | Lam C.S.P.,Boston University | Liu X.,Boston University | Yang Q.,Boston University | And 8 more authors.
Circulation: Cardiovascular Genetics | Year: 2010

Background - Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited. Methods and Results - We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001). Conclusions-Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF. © 2010 American Heart Association, Inc.

Imboden M.,SwissTPH | Imboden M.,University of Basel | Bouzigon E.,French Institute of Health and Medical Research | Bouzigon E.,Fondation Jean Dausset Center dEtude du Polymorphisme Humain | And 55 more authors.
Journal of Allergy and Clinical Immunology | Year: 2012

Background: Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung function. Objective: We conducted the first genome-wide association study on the age-related decrease in FEV 1 and its ratio to forced vital capacity (FVC) stratified a priori by asthma status. Methods: Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV 1 and FEV 1/FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study). Results: Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV 1 decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 × 10 -6; replication, P =.03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV 1/FVC ratio decrease in asthmatic participants (P = 5.3 × 10 -8), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline. Conclusions: Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status. © 2012 American Academy of Allergy, Asthma & Immunology.

Foster M.C.,Blood Institutes Framingham Heart Study | Foster M.C.,Harvard University | Foster M.C.,U.S. National Institutes of Health | Hwang S.-J.,Blood Institutes Framingham Heart Study | And 7 more authors.
BMC Nephrology | Year: 2011

Background: Renal sinus fat may mediate obesity-related vascular disease, although this fat depot has not been assessed in a community-based sample. We sought to develop a protocol to quantify renal sinus fat accumulation using multi-detector computed tomography (MDCT). Methods. Protocol development was performed in participants in the Framingham Offspring cohort who underwent MDCT. Volumetric renal sinus fat was measured separately within the right and left kidneys, and renal sinus fat area within a single MDCT scan slice was measured in the right kidney. Due to the high correlation of volumetric and single-slice renal sinus fat in the right kidney (Pearson correlation [r] = 0.85, p < 0.0001), we optimized a single-slice protocol to capture renal sinus fat in the right kidney alone. Pearson correlation coefficients were used to compare to assess the correlation of volumetric and single-slice renal sinus fat in the right kidney with other measures of adiposity. Inter- and intra-reader reproducibility was assessed using intra-class correlation coefficients. Results: Single-slice measurements were obtained in 92 participants (mean age 60 years, 49% women, median renal sinus fat 0.43 cm 2). Intra- and inter-reader intra-class correlation coefficients were 0.93 and 0.86, respectively. Single-slice renal sinus fat was correlated with body mass index (r = 0.35, p = 0.0006), waist circumference (r = 0.31, p = 0.003), and abdominal visceral fat (r = 0.48, p < 0.0001). Similar correlations were observed for volumetric renal sinus fat in the right kidney. Conclusions: Measuring renal sinus fat is feasible and reproducible using MDCT scans in a community-based sample. © 2011 Foster et al; licensee BioMed Central Ltd.

Yang Q.,Boston University | Yang Q.,Blood Institutes Framingham Heart Study | Wu H.,Boston University | Wu H.,Wentworth Institute of Technology | And 4 more authors.
Genetic Epidemiology | Year: 2010

Multivariate phenotypes are frequently encountered in genome-wide association studies (GWAS). Such phenotypes contain more information than univariate phenotypes, but how to best exploit the information to increase the chance of detecting genetic variant of pleiotropic effect is not always clear. Moreover, when multivariate phenotypes contain a mixture of quantitative and qualitative measures, limited methods are applicable. In this paper, we first evaluated the approach originally proposed by O'Brien and by Wei and Johnson that combines the univariate test statistics and then we proposed two extensions to that approach. The original and proposed approaches are applicable to a multivariate phenotype containing any type of components including continuous, categorical and survival phenotypes, and applicable to samples consisting of families or unrelated samples. Simulation results suggested that all methods had valid type I error rates. Our extensions had a better power than O'Brien's method with heterogeneous means among univariate test statistics, but were less powerful than O'Brien's with homogeneous means among individual test statistics. All approaches have shown considerable increase in power compared to testing each component of a multivariate phenotype individually in some cases. We apply all the methods to GWAS of serum uric acid levels and gout with 550,000 single nucleotide polymorphisms in the Framingham Heart Study. © 2010 Wiley-Liss, Inc.

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