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Molecular Basis of Complex Traits

  1. Constantin Polychronakos

Published Online: 15 SEP 2011

DOI: 10.1002/9780470015902.a0021448



How to Cite

Polychronakos, C. 2011. Molecular Basis of Complex Traits. eLS. .

Author Information

  1. McGill University Health Centre, Montréal, QC, Canada

Publication History

  1. Published Online: 15 SEP 2011


Most genetically determined differences between individuals, including (but not limited to) susceptibility to specific diseases, depend on functional variation at multiple genes (loci). The frequency of these variants (alleles) in the general population varies from common to rare. The contribution of most common alleles, each in isolation, to disease risk is weak. Most uncommon and rare alleles have not been studied to date and some may have strong effects on disease risk even if they contribute to disease cause each in a small subset of cases. This mixture of strong and weak effects by common and rare alleles is referred to as allelic architecture. Defining the allelic architecture of each disease will be the first step towards using an individual's genetic profile to individualise the molecular diagnosis within a group of cases that all bear the same clinical diagnostic label.

Key Concepts:

  • Most diseases and other human traits have statistically significant familial clustering, indicating the involvement of genetic susceptibility.

  • Genetic susceptibility to most diseases is determined by a large number of gene variants (loci).

  • Disease-associated variants may change the sequence of the protein product, or the control of its transcription, RNA stability or translational efficiency.

  • Most known loci have a weak genetic association with the disease or trait.

  • A genetic association may be weak because of weak biology, or because the associated allele is merely an imperfect marker for an untested rare allele with strong effect.

  • The discovery, among low-frequency alleles, of those that have the strongest effects, is the next frontier in the genetics of complex traits and the greatest promise to personalised medicine.


  • complex trait;
  • missing heritability;
  • allele frequency;
  • relative risk;
  • nonsynonymous;
  • genetic marker;
  • linkage disequilibrium;
  • allelic architecture;
  • genome-wide