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Diabetes 56:2844-2848, 2007
DOI: 10.2337/db07-1324
© 2007 by the American Diabetes Association
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Commentary

Genome-Wide Association

Which Do You Want First: the Good News, the Bad News, or the Good News?

Kent D. Taylor1,2, Jill M. Norris3, and Jerome I. Rotter1,2,4

1 Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
2 Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
3 Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
4 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California

Address correspondence and reprint requests to Jerome I. Rotter, Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Suite 665, West Los Angeles, California 90048-1804. E-mail: jerome.rotter@cshs.org

Abbreviations: GWA, genome-wide association; SNP, single nucleotide polymorphism

The first 300 words of the full text of this article appear below.

It has long been appreciated that there is a genetic component to type 2 diabetes, but progress in gene finding has been slow because the genetic component is complex. Accumulating data on various diabetes-related phenotypes suggest that so-called "type 2 diabetes" is likely a collection of many diseases due to varying but often overlapping underlying mechanisms. As such, the search for the once hoped-for simple genetic basis of type 2 diabetes has proved elusive.

This year marks the application of the next gene-finding tool to the study of type 2 diabetes, the genome-wide association study (GWA). This type of study is the logical extension of the candidate gene association study, an approach in which a few (1–20 or so) single nucleotide polymorphisms (SNPs) within a single gene are tested for association with the phenotype of interest. By that approach, the candidate gene is chosen based on biochemistry or physiology related to that phenotype. The candidate gene approach has identified some genes but has not yielded the definitive picture of the genetic contribution to type 2 diabetes (Table 1; reviewed in [1]).


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  		TABLE 1 Genetic factors for type 2 diabetes

 
In contrast, the GWA approach tests every gene by testing the association of SNPs in every known gene (~100,000 SNPs) or in both known genes and in regions outside of genes throughout the genome (~300,000 to 1 million). The GWA is therefore not biased by a priori assumptions based on prior observations of the phenotype (e.g., kinetics of insulin signaling, glucose-mediated insulin secretion, etc). Therefore, the strength of the GWA is that it has the potential to identify genes of high genetic effect that were previously unsuspected as candidates. The latter might be because little was known about the genes previously or because investigators simply had not . . . [Full Text of this Article]

Genotyping with different SNP ensembles.
Extension into other ethnic groups.
Analysis of subphenotypes.

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S. S. Rich, J. M. Norris, and J. I. Rotter
Genes Associated With Risk of Type 2 Diabetes Identified by a Candidate-Wide Association Scan: As a Trickle Becomes a Flood
Diabetes, November 1, 2008; 57(11): 2915 - 2917.
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