Epidemiological and Genetic Studies of Body Mass Index

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.