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closeDisagreement over extension of LD
Posted by freeseek on 27 Jan 2010 at 01:39 GMT
The distance over which synthetic associations occur also offers an alternative explanation to the increasingly common observation of rare variants that occur within the vicinity of a GWAS signal but cannot explain that signal entirely. A simple explanation for such observations is that extending the sequencing to at least 4 Mb and ideally up to 10 Mb around the GWAS signal would pick up other rare variants.
http://plosbiology.org/article/info:doi/10.1371/journal.pbio.1000294#article1.body1.sec3.p6
I think the Sickle Cell Anemia case is not a good one to make this conclusion. The analysis was performed in African Americans, so most of the LD will be due to ancestry. Furthermore, even if ancestry correction is performed among cases and controls, it still holds that the Sickle Cell Anemia variant has been recently naturally selected, which means the variant has reach high frequency in a short time, without giving recombination the chance to set nearby alleles to a state of linkage equilibrium with the variant.