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Science 20 December 2002:
Vol. 298. no. 5602, pp. 2345 - 2349
DOI: 10.1126/science.1076641
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Review

GENETICS:
Finding Genes That Underlie Complex Traits

Anne M. Glazier,1 Joseph H. Nadeau,2* Timothy J. Aitman1*

Phenotypic variation among organisms is central to evolutionary adaptations underlying natural and artificial selection, and also determines individual susceptibility to common diseases. These types of complex traits pose special challenges for genetic analysis because of gene-gene and gene-environment interactions, genetic heterogeneity, low penetrance, and limited statistical power. Emerging genome resources and technologies are enabling systematic identification of genes underlying these complex traits. We propose standards for proof of gene discovery in complex traits and evaluate the nature of the genes identified to date. These proof-of-concept studies demonstrate the insights that can be expected from the accelerating pace of gene discovery in this field.

1 Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College Faculty of Medicine, Ducane Road, London W12 0NN, UK.
2 Department of Genetics and Center for Computational Genomics, Case Western Reserve University, Cleveland, OH 44106, USA.
*   To whom correspondence should be addressed. E-mail: jhn4{at}po.cwru.edu, t.aitman{at}csc.mrc.ac.uk

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Autonomic Nervous System Pharmacogenomics: A Progress Report.
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Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition.
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Quantitative Trait Loci Specifying the Response of Body Temperature to Dietary Restriction.
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J. Gerontol. A Biol. Sci. Med. Sci. 59, B118-125
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Application of chromosomal substitution techniques in gene-function discovery.
A. W. Cowley Jr, R. J. Roman, and H. J. Jacob (2004)
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Functional genomics in rodent models of hypertension.
M. W. McBride, F. J. Charchar, D. Graham, W. H. Miller, P. Strahorn, F. J. Carr, and A. F. Dominiczak (2004)
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