Abstract
Human geneticists are currently in the middle of a race. Thanks to a new technology in the form of 'genome-wide chips', investigators can potentially find many novel disease genes in one large experiment. Type 2 diabetes has been hot out of the blocks with six recent publications that together provide convincing evidence for six new gene regions involved in the condition. Together with candidate approaches, these studies have identified 11 confirmed genomic regions that alter the risk of type 2 diabetes in the European population. One of these regions, the fat mass and obesity associated gene (FTO), represents by far the best example of an association between common variation and fat mass in the general population.
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Acknowledgements
I would like to thank specifically M. Weedon and R. Freathy for help and advice on the article, and more generally all my colleagues in Exeter and Oxford with whom I worked on the UK type 2 diabetes genome-wide study.
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Glossary
- Body mass index
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(BMI). BMI is an easy way of estimating how fat people are. It is measured as weight in kilograms divided by height in metres squared (kg/m2). A BMI < 25 is considered normal, ≥25 to <30 overweight and ≥30 obese.
- Deep sequencing
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Systematic sequencing of contiguous sequence in many individuals.
- Linkage disequilibrium
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A measure of associations between alleles at different loci, which indicates whether particular haplotypes are more common than expected. We use the r2 definition, which equates directly to power. For example, an r2 of 0.8 equates to 80% power.
- Odds ratio
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A measurement of association in case–control studies, defined as the odds of exposure to the susceptibility allele in cases compared with that in controls. If the odds ratio is significantly greater than one, then the allele is associated with an increased risk of the disease.
- Population admixture
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A process that leads to a composite gene pool in which at least some individuals come from more than one population.
- r2 value
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A standard way of quantifying the degree of correlation between polymorphisms. An r2 of 1 indicates that the two variants would give exactly the same genotypes for an individual.
- Sibling relative risk
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The chance of being affected by a condition if a sibling is affected, relative to a member of the general population. Siblings of people with type 2 diabetes are three to four times more likely to develop the illness than others.
- Tagging
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Identifying subsets of markers ('tags') that describe patterns of association or haplotypes among larger marker sets. Tag SNPs are single nucleotide polymorphisms that are correlated with, and therefore can serve as a proxy for, common variation in a region that has not been directly analysed.
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Frayling, T. Genome–wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8, 657–662 (2007). https://doi.org/10.1038/nrg2178
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DOI: https://doi.org/10.1038/nrg2178
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