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Candidate-gene approaches for studying complex genetic traits: practical considerations

Nature Reviews Genetics volume 3, pages 391–397 (2002)Cite this article

Abstract

Association studies with candidate genes have been widely used for the study of complex diseases. However, this approach has been criticized because of non-replication of results and limits on its ability to include all possible causative genes and polymorphisms. These challenges have led to pessimism about the candidate-gene approach and about the genetic analysis of complex diseases in general. We believe that these criticisms can be usefully countered with an appeal to the principles of epidemiological investigation.

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Figure 1: Haplotypes and linkage disequilibrium in single-nucleotide-polymorphism selection.

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Acknowledgements

We thank members of the Myers laboratory and the Stanford Human Genome Center for their support. H.K.T., N.J.R. and R.M.M are supported by the National Institutes of Health and the Reynolds Foundation.

Author information

Authors and Affiliations

  1. Department of Health Research and Policy, and the Department of Genetics, Stanford University School of Medicine, Stanford, 94305-5120, California, USA

    Holly K. Tabor

  2. Department of Genetics, Stanford University School of Medicine and the Division of Research, Kaiser Permanente, Oakland, 94611, California, USA

    Neil J. Risch

  3. Department of Genetics, Stanford University School of Medicine,

    Richard M. Myers

Authors
  1. Holly K. Tabor
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  2. Neil J. Risch
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  3. Richard M. Myers
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Corresponding author

Correspondence to Richard M. Myers.

Related links

Related links

DATABASES

CancerNet

breast cancer

LocusLink

BRCA1

MECP2

OMIM

Crohn disease

Rett syndrome

FURTHER INFORMATION

Allele Frequency Project

Celera

Genaissance

HGVbase (and SNP-related databases)

Human Gene Mutation Database

HGMD locus-specific mutation databases

Glossary

CONFOUNDING

The distortion of a measure of association, because of the association of other non-intermediate factors with both the variable of interest and the outcome of interest.

HAPLOTYPE

A combination of alleles at different sites on a single chromosome.

HERITABILITY

The proportion of the phenotypic variance due to genetic variance.

LINKAGE DISEQUILIBRIUM

A population association among alleles at two or more loci. It is a measure of co-segregation of alleles in a population.

MISCLASSIFICATION

Errors in the classification of individuals by phenotype, exposures or genotype that can lead to errors in results. The probability of misclassification can be the same across all groups in a study (non-differential) or vary among groups (differential).

RECALL BIAS

Bias in results due to systematic differences in the accuracy or completeness of recall of past exposures or family history.

RELATIVE RISK

The ratio of the risk of the phenotype among individuals with a particular exposure, genotype or haplotype to the risk among those without that exposure, genotype or haplotype.

SELECTION BIAS

A bias in results due to systematic differences between those who are selected for study and those who are not selected.

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Tabor, H., Risch, N. & Myers, R. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 3, 391–397 (2002). https://doi.org/10.1038/nrg796

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