Genetic architecture of quantitative traits and complex diseases

Curr Opin Genet Dev. 2013 Dec;23(6):678-83. doi: 10.1016/j.gde.2013.10.008. Epub 2013 Nov 26.


More than 150 years after Mendel discovered the laws of heredity, the genetic architecture of phenotypic variation remains elusive. Here, we discuss recent progress in deciphering how genotypes map onto phenotypes, sources of genetic complexity, and how model organisms are illuminating general principles about the relationship between genetic and phenotypic variation. Moreover, we highlight insights gleaned from large-scale sequencing studies in humans, and how this knowledge informs outstanding questions about the genetic architecture of quantitative traits and complex diseases. Finally, we articulate how the confluence of technologies enabling whole-genome sequencing, comprehensive phenotyping, and high-throughput functional assays of polymorphisms will facilitate a more principled and mechanistic understanding of the genetic architecture of phenotypic variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Models, Genetic
  • Phenotype
  • Quantitative Trait Loci / genetics*