Genetic architecture: the shape of the genetic contribution to human traits and disease

Nat Rev Genet. 2018 Feb;19(2):110-124. doi: 10.1038/nrg.2017.101. Epub 2017 Dec 11.


Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.

Publication types

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

MeSH terms

  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics*
  • Genome-Wide Association Study
  • Humans
  • Multifactorial Inheritance*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait, Heritable*