domingo, 23 de enero de 2011

PLoS Biology Announces Genome Wide Association Study (GWAS) Series



PLoS Biology Announces Genome Wide Association Study (GWAS) Series
Main Category: Biology / Biochemistry
Article Date: 19 Jan 2011 - 0:00 PST



The current working assumption is that many diseases with a genetic component (those that seem to run in families) are caused by DNA variants that are common in the population - the so called "common disease, common variant" model. Those with the disease have an unfortunate combination of variants - much like being dealt a poor hand from a standard deck of cards. If this were the case, then performing a Genome wide association study (GWAS) which compares DNA variants present in large numbers of sufferers with those present in healthy individuals would reveal the causative DNA variants.

Of the now more than 700 genome wide association studies (GWAS) published, at least 2,000 common variants have been linked to over a hundred diseases. Nevertheless, people with the supposed disease-predisposing alleles are only slightly more likely to get the disease than those without. Larger scale studies have revealed more disease genes, but usually with smaller effect on overall disease risk.

So where are the genes accounting for major predisposition to disease? In January 2010, PLoS Biology published a paper by Goldstein and colleagues arguing rare variants had much greater impact on disease risk then previously supposed. This generated a huge amount of controversy - not least because it would undermine the usual strategy of looking for disease genes. To further investigate the matter, PLoS Biology is publishing two critiques of the Goldstein article (by Anderson et al. and Wray et al.) and a response from the authors of the original article next week. To learn more about this GWAS series, see the Editorial "Common disease - are causative alleles common or rare?" by PLoS Biology Editor Dr. Robert Shields.

Funding for Anderson et al: This work was funded by the Wellcome Trust (CAA: WT091745/Z/10/Z, JCB:WT089120/Z/09/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding for Wray et al: We acknowledge funding from the Australian National Health and Medical Research Council (grants 389892, 442915, 496688, 613672, and 613601) and the Australian Research Council (grants DP0770096 and DP1093900 and Future Fellowship to NRW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests statement: The authors declare that no competing interests exist.

Citations: Anderson CA, Soranzo N, Zeggini E, Barrett JC (2011) Synthetic Associations Are Unlikely to Account for Many Common Disease Genome-Wide Association Signals. PLoS Biol 9(1): e1000580. doi:10.1371/journal.pbio.1000580

Wray NR, Purcell SM, Visscher PM (2011) Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results. PLoS Biol 9(1): e1000579. doi:10.1371/journal.pbio.1000579

Goldstein DB (2011) The Importance of Synthetic Associations Will Only Be Resolved Empirically. PLoS Biol 9(1): e1001008. doi:10.1371/journal.pbio.1001008

Shields R (2011) Common Disease: Are Causative Alleles Common or Rare? PLoS Biol 9(1): e1001009.doi:10.1371/journal.pbio.1001009

Source: PLoS Biology
PLoS Biology Announces Genome Wide Association Study (GWAS) Series

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