A polygenic basis for late-onset disease

Trends Genet. 2003 Feb;19(2):97-106. doi: 10.1016/s0168-9525(02)00033-1.


The biological basis of late-onset disease has been shaped by genetic factors subject to varying degrees of evolutionary constraint. Late-onset traits are not only more sensitive to environmental variation, owing to the breakdown of homeostatic mechanisms, but they also show higher levels of genetic variation than traits directly influencing reproductive fitness. The origin and nature of this variation suggests that current strategies are poorly suited to identifying genes involved in many complex diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset*
  • Alleles
  • Animals
  • Arteriosclerosis / genetics
  • Environment
  • Genetic Variation
  • Genetics, Population
  • Humans
  • Kinetics
  • Multifactorial Inheritance*
  • Mutation
  • Phenotype
  • Quantitative Trait, Heritable