Defining an Obesity QTL on Chromosome 3q
Condition: Cardiovascular Diseases; Heart Diseases; Obesity
MeSH terms: Cardiovascular Diseases; Heart Diseases; Obesity
Study type: Observational

Summary: 
      To investigate the genetic basis of obesity by fine mapping an obesity quantitative trail
      linkage (QTL) linked to chromosome 3q.
    

Detailed description: 
      BACKGROUND:

      In the last several decades obesity has emerged as a major public health threat. While
      prevention through lifestyle change is the only long-term solution, better understanding of
      the physiologic mechanisms would greatly assist development of drugs and targeted prevention.
      Obesity is a highly heritable condition and while genes must account for a substantial
      proportion of individual susceptibility they have eluded detection. Powerful new genetic and
      genomic tools now permit comprehensive evaluation of candidate genes, including all genes
      under linkage peaks. These tools include new genomic resources (the human genome sequence,
      databases of common SNPs, and the haplotype map), rapid and inexpensive discovery and
      genotyping and new analytic methods (haplotype-based association and admixture mapping).

      DESIGN NARRATIVE:

      In a large African American family set Dr. Zhu and colleagues have obtained strong linkage
      evidence for obesity on chromosome 3q (combined LOD score = 3.7). A prime candidate
      (adiponectin) lies near this peak. They propose to follow up that finding by combining the
      epidemiologic data with high-throughput genotyping and move from linkage to association
      analysis. The results for this QTL will be evaluated within the available environmental
      factors to assess potential gene-environment and gene-gene interactions. The available
      phenotypes include body composition, resting metabolic rate, physical activity, plasma
      insulin, glucose, and leptin. In a family-based design they will examine the linkage peak
      centered on position 188 cM on chromosome 3q (20 Cm 1-LOD support interval), with the
      following step-wise strategy: (a) Genotype 200 single nucleotide polymorphisms (SNPs) in this
      region on 300 families (1,000 individuals); (b) Conduct linkage, linkage disequilibrium and
      admixture mapping to potentially further narrow the region; and (c) Conduct resequencing and
      haplotype-based association studies for all candidate genes under the peak. Statistical
      analysis incorporating intermediate phenotypes and environmental covariates will be used to
      characterize potential gene x gene or gene x environment interactions. Replication will be
      tested in additional populations of African and European origin.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Maywood cohort DNA samples were obtained from a larger cohort of families enrolled in the
        studies of blood pressure at Loyola University in Maywood, IL. The survey enrolled a
        representative random sample of the population between the ages of 18 and 74, regardless of
        obesity phenotype. A subcohort of 775 unrelated participants was selected and oversampled
        at the upper and lower ends of the BMI distribution to increase the power.

        Nigerian cohort Study participants were recruited from Igbo-Ora and Ibadan in southwest
        Nigeria as part of a long-term study on the environmental and genetic factors underlying
        hypertension. The sample comprised 1098 unrelated adults with normal or elevated blood
        pressure and 155 unrelated participants from Ibadan with elevated blood pressure recruited
        as controls in the Africa-America Diabetes Mellitus (AADM) study.