Complex Genetic Systems and Diseases


Most traits of interest in medical (including psychiatric) contexts are complex traits, generally of multifactorial aetiology including genetic factors. These genetic factors may include coding and noncoding sequences (with the variation in the latter being the dominant mode of human genetic variation). Epigenetic factors may also be involved in the aetiology of diseases. The study of genetic aspects of complex traits presents a level of conceptual and technical difficulties not seen elsewhere in genetics. New molecular techniques, especially those that have emerged in the post‐genomic era, provide promise for a solution to these problems. Genome‐wide association studies have provided evidence for the common disease–common variant hypothesis. However, other studies have noted the importance of rare variants including some with severe effects. The importance of epigenetic factors has recently come to be recognised. Over all, the advances of genomics and the post‐genomic era have underscored the complexity of disease aetiology in most cases.

Key Concepts:

  • Disease traits are a result of complex developmental interactions between genomic and environmental factors.

  • Complex genetic traits are those that fall between simple Mendelising traits and the quantitative (continuously varying) traits traditionally studied by the methods of quantitative genetics.

  • Many disease traits are complex genetic systems of this sort.

  • The contribution of classical genetics (including quantitative genetics) to the study of most disease traits has been modest.

  • In contrast, recent molecular methods including allele sharing, quantitative trait locus mapping and allelic association studies show more promise.

  • Genome‐wide allelic association studies have provided a wealth of new insight and considerable support for the ‘common disease–common variant’ model of disease aetiology.

  • However, rare genetic variants may also be important for the aetiology of some diseases including psychiatric ones.

  • Because of the social and political ramifications of genetic explanations, care must be taken in imputing genetic etiologies to diseases.

Keywords: genetic disease; genetic aetiology; genome‐wide association studies; common disease–common variant; complex traits; polygenic traits; genomics; genetic reductionism


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Sarkar, Sahotra(Apr 2012) Complex Genetic Systems and Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005887.pub2]