Segregation and linkage analysis for longitudinal measurements of a quantitative trait

BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S21. doi: 10.1186/1471-2156-4-S1-S21.

Abstract

We present a method for using slopes and intercepts from a linear regression of a quantitative trait as outcomes in segregation and linkage analyses. We apply the method to the analysis of longitudinal systolic blood pressure (SBP) data from the Framingham Heart Study. A first-stage linear model was fit to each subject's SBP measurements to estimate both their slope over time and an intercept, the latter scaled to represent the mean SBP at the average observed age (53.7 years). The subject-specific intercepts and slopes were then analyzed using segregation and linkage analysis. We describe a method for using the standard errors of the first-stage intercepts and slopes as weights in the genetic analyses. For the intercepts, we found significant evidence of a Mendelian gene in segregation analysis and suggestive linkage results (with LOD scores >or= 1.5) for specific markers on chromosomes 1, 3, 5, 9, 10, and 17. For the slopes, however, the data did not support a Mendelian model, and thus no formal linkage analyses were conducted.

Publication types

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

MeSH terms

  • Adult Children
  • Blood Pressure / genetics
  • Blood Pressure / physiology
  • Chromosome Mapping / methods
  • Chromosome Mapping / statistics & numerical data
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Cohort Studies
  • Female
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Humans
  • Linkage Disequilibrium / genetics*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Quantitative Trait Loci / genetics
  • Quantitative Trait, Heritable*
  • Systole

Substances

  • Genetic Markers