Comparison between two analytic strategies to detect linkage to obesity with genetically determined age of onset: the Framingham Heart Study

BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S90. doi: 10.1186/1471-2156-4-S1-S90.

Abstract

Background: Genes have been found to influence the age of onset of several diseases and traits. The occurrence of many chronic diseases, obesity included, appears to be strongly age-dependent. However, an analysis of potential age of onset genes for obesity has yet to be reported. There are at least two analytic methods for determining an age of onset gene. The first is to consider a person affected if they possess the trait before a certain age (an early age of onset phenotype). The second is to define the phenotype based on the residual from a survival analysis.

Results: No regions provided evidence for linkage at the more stringent level of p < 0.001. However, five regions showed consistent suggestive evidence for linkage (one marker with p < 0.01 and a second contiguous marker at p < 0.05). These regions were chromosome 1 (280-294 cM) and chromosome 16 (56-64 cM) for overweight using the survival analysis residual method and chromosome 13 (102-122 cM), chromosome 17 (127-138 cM), and chromosome 19 (23-47 cM) for obese before age 35.

Conclusion: Only one region (chromosome 19 at 23-47 cM) showed somewhat consistent results between the two analytic methods. Potential reasons for inconsistent results between the two methods, as well as their strengths and weaknesses, are discussed. The use of both methods together to explore the genetics of the age of onset of a trait may prove to be beneficial in determining a gene that is linked only to an early age of onset phenotype versus one that determines age of onset through all age groups.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Adult Children
  • Age of Onset
  • Chromosome Mapping / statistics & numerical data
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 16 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Cohort Studies
  • Female
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease / epidemiology
  • Humans
  • Male
  • Obesity / epidemiology*
  • Obesity / genetics*
  • Pedigree
  • Phenotype
  • Survival Analysis