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

doi:10.1038/NRG796

Journal ArticleDOI

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

Holly K. Tabor, +2 more

- 01 May 2002 -

Nature Reviews Genetics

- Vol. 3, Iss: 5, pp 391-397

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TLDR

The candidate-gene approach has been criticised because of non-replication of results and limits on its ability to include all possible causative genes and polymorphisms as discussed by the authors, and these challenges have led to pessimism about the candidate gene approach and about the genetic analysis of complex diseases in general.

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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‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?

George Davey Smith, +1 more

- 01 Feb 2003 -

International Journal of Epidemiology

TL;DR: Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.

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Journal ArticleDOI

Genome-wide association studies for common diseases and complex traits

Joel N. Hirschhorn, +4 more

- 01 Feb 2005 -

Nature Reviews Genetics

TL;DR: Genome-wide association studies will soon become possible, and could open new frontiers in the understanding and treatment of disease, however, the execution and analysis of such studies will require great care.

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Journal ArticleDOI

Mendelian randomization: using genes as instruments for making causal inferences in epidemiology.

Debbie A Lawlor, +4 more

- 15 Apr 2008 -

Statistics in Medicine

TL;DR: The use of germline genetic variants that proxy for environmentally modifiable exposures as instruments for these exposures is one form of IV analysis that can be implemented within observational epidemiological studies and can be considered as analogous to randomized controlled trials.

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Journal ArticleDOI

Landscape genetics: combining landscape ecology and population genetics

Stéphanie Manel, +3 more

- 01 Apr 2003 -

Trends in Ecology and Evolution

TL;DR: A new approach has emerged for analyzing spatial genetic data without requiring that discrete populations be identified in advance, and promises to facilitate the understanding of how geographical and environmental features structure genetic variation at both the population and individual levels.

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Journal ArticleDOI

Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.

Kirk E. Lohmueller, +5 more

- 13 Jan 2003 -

Nature Genetics

TL;DR: It is concluded that there are probably many common variants in the human genome with modest but real effects on common disease risk, and that studies using large samples will convincingly identify such variants.

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References

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Journal ArticleDOI

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Eric S. Lander, +248 more

- 15 Feb 2001 -

Nature

TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.

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J. Craig Venter, +272 more

- 16 Feb 2001 -

Science

TL;DR: Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.

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Journal ArticleDOI

Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease

Jean-Pierre Hugot, +21 more

- 31 May 2001 -

Nature

TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.

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Journal ArticleDOI

The Future of Genetic Studies of Complex Human Diseases

Neil Risch, +1 more

- 13 Sep 1996 -

Science

TL;DR: The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult as mentioned in this paper, and Risch and Merikangas proposed that they can best accomplish this goal by combining the power of the human genome project with association studies.

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