Epidemiological and Genetic Studies of Body Mass Index
Condition: Cardiovascular Diseases; Obesity; Heart Diseases
MeSH terms: Cardiovascular Diseases; Heart Diseases
Study type: Observational

Summary: 
      To identify genes involved in obesity.
    

Detailed description: 
      BACKGROUND:

      Increased levels of body mass index (BMI) are associated with increased mortality and
      morbidity from cardiovascular disease, hypertension, diabetes and other disorders. The
      frequency of obesity and its associated health-related problems is increasing in the American
      population.

      DESIGN NARRATIVE:

      The study builds upon a two-stage genome scan for BMI performed in the NHLBI Family Heart
      Study (FHS). In the first, 101 pedigrees were examined with 1027 persons genotyped and a LOD
      of 2.2 was found on chromosome 7. In stage 2, 135 sibships of 380 persons were examined , and
      a LOD of 3.2 was found for the same locus. Compelling linkage was found in the combined study
      (LOD = 4.9, chr 7q31.3, 137cM). The LOD or logarithm of odds is a statistical estimate of
      whether two loci (the sites of genes) are likely to lie near each other on a chromosome and
      are therefore likely to be inherited together as a package.

      A novel strategy will be used which combines three cutting edge methods: (1) Regression Tree
      analyses to identify a homogenous subset of families with evidence for BMI linkage to 7q31.3;
      (2) DNA pooling of samples from linked versus unlinked families; and (3) quantitative PCR of
      DNA pools for very high-density single nucleotide polymorphism (SNP) mapping. The combination
      of these methods will permit a cost effective approach for the identification of genetic
      polymorphisms in linkage disequilibrium with BMI, and has the potential to become a widely
      adopted method for gene localization of complex traits.

      The study was extended through January, 2008 to show compelling evidence for a haplotype in
      the 5' region of the Leptin gene (p<0.00005) influencing BMI among men in the sample. The
      study will further demonstrate that the responsible gene in this region is not Leptin. SNP
      and haplotype association studies implicate three strong candidate loci and other loci also
      warrant additional study. The study will confirm SNP association in an independent study of
      200 families showing linkage to the same position (from Dr. R. Arlen Price's group). Those
      loci with confirmed association will be further characterized by sequencing, genotyping new
      polymorphisms, and gene expression studies to identify the responsible genes.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        In this study the amount of the gene product in the different tissue samples for the
        candidate genes will be analyzed. The study design is to compare the expression of genes in
        cell lines with different genetic variants for genes hypothesized to influence obesity or
        body mass index and located on chromosome 7. Genetic variants which distinguish the
        expression of genes will be investigated in other samples derived from this or similar
        studies. No drug intervention. No patient contacts for this research. No subject
        participation for this research, which is carried out on existing cell lines, data and DNA.
        The study will continue until the gene is found or we fail to obtain funding renewal. The
        expected duration of this component of our study is approximately 4 years.
      
Biospecimen description: 
      This study ended years ago, I do not know why I am being asked to update it as a clinical
      trial. It was never a clinical trial.