L Adrienne Cupples

..When testing linkage or association, the conditional logistic regression method was more powerful than FBAT...

..We evaluated the performance of this method using independent test data sets for up to 100 replicates...

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..Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes...

..We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-epsilon4 carrier status and ethnicity...

..Further evaluation of the type I error rate and power of the FDR approaches for higher linkage disequilibrium and for haplotype analyses is warranted...

..Moreover, information on disease severity appears to be useful to improve the ability to detect associations between markers and disease loci...

..However, the power of these tests appears to be inflated over the complete information case due to an excess of heterozygous parents in dyads...

..We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets...

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..Nevertheless, Group 14 found that these methods offered strategies to gain a better understanding of the complex pathways by which disease develops...

..Are these approaches now passé? Here we discuss the role of family studies in modern genetics research, using results from the Framingham Heart Study as examples...

..However, replication has been low. Our aim was to study interaction among a functional APOA2 polymorphism, food intake, and body mass index (BMI) in independent populations to replicate findings and to increase their evidence level...

..To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women...

..Applying the i-TDT to the Framingham Heart Study data, we found that the apolipoprotein E (APOE) gene is significantly linked and associated with cross-sectional measures and longitudinal changes in total cholesterol...

..APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels...

..Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association...

..To explore potential mechanisms by which these gene variants may contribute to cardiovascular disease, we tested the hypothesis that the polymorphisms were associated with endogenous steroid hormone levels...

..Such interactions might also influence trait-locus associations and may be useful to consider in diabetes genome-wide association studies...

..The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women...

..Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes...

..The interaction does not appear to be mediated through effects on high-density lipoprotein cholesterol...

..The alteration of a binding site of the deregulator of extracellular matrix HOXA7 warrants further investigation...

..We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it...

..Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure...

..We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study...

..We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community...

..Left ventricular (LV) mass is a biomarker of long-standing exposure to cardiovascular disease risk factors. We hypothesized that LTL is related inversely to LV mass...

..Elevated PAI-1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels...

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..Moderate intake of alcohol has been reported to have beneficial effects on bone. However, different classes of alcoholic beverages have not been investigated...

..Few studies have examined the association between carotenoid intake (other than beta-carotene) and bone mineral density (BMD)...

..53, 1.00; p(trend) = 0.03). In contrast, no association was present in men (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 1.14, 95% confidence interval: 0.84, 1.56; p(trend) = 0.55)...

..We demonstrate our methods on simulated data and on fasting insulin, a quantitative trait measured in the Framingham Heart Study...

..Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits...

..Using comprehensive linkage disequilibrium mapping, we genotyped single nucleotide polymorphisms (SNPs) in ADIPOQ to evaluate the association of common variants with adiponectin levels and risk of diabetes...

..We tested the hypothesis that knowledge of these loci allows better prediction of risk than knowledge of common phenotypic risk factors alone...

..In women, the -1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03-3.34; P = 0.04), in agreement with the association of this SNP with higher RLPs...

..30T-c.454-397T-c.454-351A haplotype (frequency, 46%), where L and S are long and short TA repeats. Our results suggest that common ESR1 polymorphisms have a significant effect on lipoprotein metabolism in women...

..Polymorphisms in estrogen receptor-alpha (ESR1) may be associated with variation in body mass index and waist circumference. However, most prior studies have been limited by sample size and power...

..The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting...

..Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants...

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..03). Further study of the linkage region and exploration of other variants in PLAGL1 are warranted to define the potential functional variants of HDL-C metabolism...

..Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk...

..We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study...

..Finally, the use of this unique sample to study genotype and environment interactions is described...

..To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis...

..Previous studies of carbohydrate quality and risk of type 2 diabetes mellitus have yielded inconsistent findings. Because diet is in part culturally determined, a study of dietary factors in US black women is of interest...

..Because white fat is a major source of IL-6 in resting individuals, we tested the hypothesis that BMI modifies the association among the IL-6 genotype, insulin resistance (IR) (measured using the homeostasis model), and risk of diabetes...

..Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure...

..The purpose of this study was to examine the link between LTL and the predisposition to atherosclerosis, as determined by carotid artery intimal medial thickness (IMT) in participants of the Framingham Offspring Study...

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..Microalbuminuria is a powerful risk factor for cardiovascular disease. It is not known whether genetic factors play a role in the expression of microalbuminuria in population-based samples...

..Our data show that the effect of the L162V polymorphism on plasma TG and apoC-III concentrations depends on the dietary PUFA, with a high intake triggering lower TG in carriers of the 162V allele...

..We compared regression-based linkage to variance components linkage across time for six quantitative traits in the real data...

..A variance components model (SOLAR) was employed in the univariate approaches. A mixed regression model with polynomials was employed in the multivariate approach and implemented in SAS/IML...

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..Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis...

..Retrospective 3-month recall of falls resulted in underreporting of falls by as much as 25% compared with daily calendars. Calendars should be considered the preferred method of ascertaining falls in longitudinal studies...

..We examined the effect of genotype disclosure in a prospective, randomized, controlled trial...

..In conclusion, the APOA5-1131T>C SNP, which is present in approximately 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women...

..We tested the hypothesis that concentrations of LpA-I and/or LpA-I:A-II HDL subclasses are significantly associated with CHD prevalence and recurrent cardiovascular events...

..We examined the association between the total homocysteine concentration and the risk of hip fracture in men and women enrolled in the Framingham Study...

..It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population...

..Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD...

..These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia...

..03 for interaction). Similar results were obtained for HDL(2)-C. In conclusion, SR-BI gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects...

..This study's main purposes were to estimate interest in such testing and to examine demographic predictors of study participation...

..Little is known about whether APOE genotype disclosure would actually prompt changes in nutrition behaviors among at-risk individuals...

..Subsequent focus on the spectrum of genetic polymorphisms in these refined regions may contribute to finding variants predisposing to osteoporosis...

..We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant...

..To use genome-wide fixed marker arrays and improved analytical tools to detect genetic associations with type 2 diabetes in a carefully phenotyped human sample...

..Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis...

..In summary, we found four independent signals in the MHC region associated with risk of SLE in African American women...

..In addition to displacing healthier beverages, colas contain caffeine and phosphoric acid (H3PO4), which may adversely affect bone...

..Several of these variants show modest evidence for association in other Caucasian populations...

..Null associations were observed among women. These results suggest a possible protective role of vitamin C for bone health in older men...

..Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels...

..We evaluated direct low density lipoprotein (LDL) cholesterol (C) and high density lipoprotein (HDL) cholesterol (C) versus standard methods using fasting plasma samples from participants in cycle 6 of the Framingham Offspring Study...

..Genes in these regions may regulate bone geometry via effects on body size. Identification and subsequent characterization of loci for bone geometry can further elucidate the genetic contributions to bone's resistance to stress...

..Clinical trials are required to isolate any putative effects of vitamin K on rates of bone loss. The target population in these trials, particularly in regard to estrogen use, may be critical, as suggested by the findings of this study...

..Diets characterized by high intakes of fruits and vegetables and low-fat dairy products (for example, the DASH diet) have been shown to reduce blood pressure in adults. The effects of similar diets on children's blood pressure are unknown...

..Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-vitamin status...

..The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients...

..Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation...

..Several nutrients are known to affect bone mineral density (BMD). However, these nutrients occur together in foods and dietary patterns, and the overall effects of dietary choices are not well understood...

..In the NAS population, men with VV were less likely to develop symptomatic CHD over the 35+ years of follow-up than were subjects without VV...

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..The protocol presents risk information as cumulative incidence curves. This article describes how these curves were estimated...

..This allele has been associated with decreased HL activity and increased HDL-C concentrations. However, the effect is variable among populations...

..Despite lack of preventive measures for AD, knowledge of APOE genotype, numerical lifetime risk, or both, influences health behavior...

..002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28-3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent...

..This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men...

..These data support the hypothesis that the INS VNTR is a genetic risk factor for type 2 diabetes, with the TT genotype accounting for about 6.6% of cases in the FHS population...

..We examined reported associations between radiographic hand osteoarthritis (OA) and single-nucleotide polymorphisms (SNP) in 2 candidate genes associated with OA in other joints: estrogen receptor alpha (ESR1) and beta (ESR2)...

..FEV1 was most influenced by the locus on chromosome 6 (logarithm of the odds favoring genetic linkage [LOD] = 2.4), whereas chromosome 21 contained markers with the strongest linkage to FVC (LOD = 2.6)...

..The most significantly associated haplotype comprised SNPs in the region spanning the -161[C/T] SNP (P=0.00009). Our results demonstrate association between AD and variants in the PON gene cluster in Caucasians and African Americans...