Metabolic syndrome (MetS), a constellation of risk factors associated with development of cardiovascular disease and Type 2 diabetes, has reached epidemic proportions in western industrialized nations. About 47 million Americans have MetS. Consequently, it has enormous impact on public health. The hallmark of MetS is a co-occurrence of obesity, dyslipidemia, carbohydrate intolerance and high blood pressure. Familial aggregation of the individual components and the composite MetS trait suggests involvement of genetic factors. However, our knowledge concerning the genetic factors underlying MetS remains largely incomplete. ? ? We propose to undertake a thorough investigation on epidemiology and genetics of MetS in an isolated population from the island of Hvar in the eastern Adriatic coast of Croatia. The value of isolated population in complex disease gene mapping has been widely documented. The study population has a high prevalence of MetS, is ethnically relevant to the general US population, with its distinct evolutionary history of recent founding by small number of Slavic founders, geographic isolation, environmental homogeneity, extended family sizes provides a unique opportunity to understand the genetics of MetS. ? ? We propose to (1) recruit 1200 individuals above 20 years of age from five villages of Hvar, collect demographic, environmental, life-style, phenotypic, relevant clinical data, and blood samples for analysis of biochemical traits and DNA; (2) conduct appropriate analyses to estimate the effects of genetic contribution to the variability of MetS as a composite trait and its constituent phenotypes; (3) conduct a whole genome scan using a panel of densely spaced, 10K, SNP markers for linkage analysis; (4) followed by pedigree-based association studies using a 'positional candidate' approach in the regions of significant linkage for identification of genetic variants associated with MetS. ? ? The study has enormous public health importance and its scientific merit is substantial with the potential of understanding the genetic etiology of MetS. We will study an ideal population for this research; our use of dense SNP markers for linkage and association is a state-of-the-art approach and has enormous promise for identifying loci and gene variants underlying MetS. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK069845-02
Application #
7272049
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Mckeon, Catherine T
Project Start
2006-08-15
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$510,187
Indirect Cost
Name
University of Cincinnati
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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Missoni, Sasa; Durakovic, Zijad; Sahay, Rashmi et al. (2013) Smoking habits according to metabolic traits in an island population of the eastern Adriatic Coast. Coll Antropol 37:745-53
Sahay, Rashmi D; Couch, Sarah C; Missoni, Sasa et al. (2013) Dietary patterns in adults from an Adriatic Island of Croatia and their associations with metabolic syndrome and its components. Coll Antropol 37:335-42
Karns, Rebekah; Succop, Paul; Zhang, Ge et al. (2013) Modeling metabolic syndrome through structural equations of metabolic traits, comorbid diseases, and GWAS variants. Obesity (Silver Spring) 21:E745-54
Deka, R; Durakovic, Z; Niu, W et al. (2012) Prevalence of metabolic syndrome and related metabolic traits in an island population of the Adriatic. Ann Hum Biol 39:46-53
Karns, Rebekah; Zhang, Ge; Sun, Guangyun et al. (2012) Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia. Ann Hum Genet 76:121-7
Zhang, Ge; Karns, Rebekah; Sun, Guangyun et al. (2012) Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height. PLoS One 7:e51211
Karns, Rebekah; Zhang, Ge; Jeran, Nina et al. (2011) Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia. Eur J Hum Genet 19:341-6
Zhang, Ge; Karns, Rebekah; Sun, Guangyun et al. (2011) Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia. PLoS One 6:e29475
Zhang, Ge; Karns, Rebekah; Narancic, Nina Smolej et al. (2010) Common SNPs in FTO gene are associated with obesity related anthropometric traits in an island population from the eastern Adriatic coast of Croatia. PLoS One 5:e10375

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