The limits of normal approximation for adult height

Eur J Hum Genet. 2021 Jul;29(7):1082-1091. doi: 10.1038/s41431-021-00836-7. Epub 2021 Mar 4.

Abstract

Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Biological Specimen Banks
  • Body Height* / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Models, Genetic
  • Multifactorial Inheritance
  • Population Surveillance
  • Quantitative Trait, Heritable*
  • Reference Values*
  • United Kingdom