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Complex disorders reloaded: causality, action, reaction, cause and effect

Molecular Psychiatry volume 9, pages 431–432 (2004)Cite this article

One of the most difficult problems in behavioral genetics is the identification of genes and alleles underlying the susceptibility and progression of complex genetic diseases. Unlike Mendelian genetic disorders, which are characterized by a single locus defect, complex disorders arise through a combination of both linear and nonlinear genetic and environmental interactions. The identification of genes contributing to the susceptibility and progression of complex human diseases has become a major focus of genetics research in the postgenomics landscape.1 Although the traditional approaches have proven successful in identifying the genetic basis of single gene disorders, similar approaches have not been very fruitful in the elucidation of complex genetic diseases.2

The notion that all individuals affected by the same genetic disorder must share common alleles in one or more distinct loci does not hold for complex disorders. Indeed, it is quite likely that multifactorial genetic diseases arise from the combined effects of tens or hundreds of interacting loci spread throughout the genome,3 which together form the metabolic and signaling pathways affected by the disease. Such a model of genetic disease suggests that numerous genotypes may result in similar phenotypes.4 Moreover, the different genetic subtypes underlying the disease state may be inadvertently blurred under classical genetic approaches when numerous affected individuals are pooled together in the hope of increasing the signal of a contributing genotype.

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Authors and Affiliations

  1. Center for Pharmacogenomics, Neuropsychiatric Institute, University California, Los Angeles, USA

    K J L Irizarry

  2. Department of Computer Science, University California, Los Angeles, USA

    S J Galbraith

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  1. K J L Irizarry
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  2. S J Galbraith
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Correspondence to K J L Irizarry.

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Irizarry, K., Galbraith, S. Complex disorders reloaded: causality, action, reaction, cause and effect. Mol Psychiatry 9, 431–432 (2004). https://doi.org/10.1038/sj.mp.4001486

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