Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from Genetic Analysis Workshop 13

Goldin, Lynn R.; Camp, Nicola J.; Keen, Kevin J.; Martin, Lisa J.; Moslehi, Roxana; Ghosh, Saurabh; North, Kari E.; Wyszynski, Diego F.; Blacker, Deborah

doi:10.1002/gepi.10288

Cited by 14 publications

(15 citation statements)

References 54 publications

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“…The accumulation of significant findings in the metabolic and the CVD groups suggests an underlying gene-gene and/or gene-environment interaction. These findings support previous reports [26,29] suggesting that the accumulation of the components defining metabolic syndrome is genetically determined, and provide additional evidence for the role of USF1 as a metabolic and cardiovascular risk factor.…”

Section: Discussionsupporting

confidence: 91%

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

et al. 2007

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Aims/hypothesis Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up.Methods Participants, born in 1920Participants, born in -1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1. Results SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p = 0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades. Conclusions/interpretation Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.

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Section: Discussionsupporting

confidence: 91%

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

et al. 2007

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“…The BEACON gene (also known as UBL5) located on chromosome 19 p has been reported to be associated with the metabolic syndrome-related endophenotypes [36]. Goldin et al [37] summarised 12 studies reporting QTLs related to the metabolic syndrome components; the QTLs were located mostly on chromosomes 1, 3, 5, 6, 7, 10, 14 and 17. Some studies have tried to locate genes responsible for the metabolic syndrome as a composite variable [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

et al. 2007

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Aims/hypothesis The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic and environmental factors influencing this cluster in a general population of twin pairs. Materials and methods A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry.Results All endophenotypes showed moderate to high heritability (0.31-0.69) and small common environmental variance (0.05-0.21). In general, genetic and phenotypic correlations between the endophenotypes were strong only within sets of physiologically similar endophenotypes, but weak to moderate for other pairs of endophenotypes. However, moderate correlations between insulin resistance indices and either obesity-related endophenotypes or triacylglycerol levels indicated that some common genetic backgrounds are shared between those components. Conclusions/interpretation We demonstrated that, in a general population, the endophenotypes associated with the metabolic syndrome apparently do not share a substantial common genetic or familial environmental background.

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“…These phenotypes tend to cluster together as the metabolic syndrome [2]. The prevailing hypothesis is that the different metabolic syndrome components are, at least in part, caused by common genes [3]. However, these metabolic states are also greatly influenced by environmental factors, such as intrauterine environment, diet and physical activity [4,5].…”

Section: Introductionmentioning

confidence: 99%

Heritability of fasting glucose levels in a young genetically isolated population

et al. 2006

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Aims/hypothesis: The heritability of fasting glucose levels in Northern European populations has been examined previously in twins and samples of small pedigrees. In this study the heritability of fasting plasma glucose (FPG) was estimated in participants in the Erasmus Rucphen Family study, who were members of a single pedigree from a young genetic isolate. We also studied the relationship between FPG and components of the metabolic syndrome. Methods: FPG, lipid, blood pressure and body composition measurements were completed for 852 participants without diabetic medication. The most significant predictors of FPG were used as covariates in heritability estimation. The sibship effect, which is a composite of genetic dominance and shared early-life environmental effects, was included as a random effect. Results: The age-and sex-adjusted heritability of log normal-transformed FPG was 36.6%. When further adjusted for metabolic risk factors, namely body composition parameters, systolic blood pressure, triglycerides and cholesterol:HDL ratio, the heritability estimate rose to 42.8%. After adjustment for the sibship effect, the additive component of heritability was estimated to be 28.3% (ageand sex-adjusted) and 24.9% (full model). Conclusions/ interpretation: Genes control a significant proportion of the variance in FPG levels. Adjustment for other metabolic risk factors did not substantially change the heritability estimate, which suggests that a large part of the variance in FPG levels is due to genes that act through pathways that are independent of those controlling body composition, blood pressure and lipid levels.

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Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from Genetic Analysis Workshop 13

Cited by 14 publications

References 54 publications

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

Heritability of fasting glucose levels in a young genetically isolated population

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