Wednesday, August 11, 2010

Tuberculosis susceptibility SNP under selective pressure

A recent publication by Thye, Vannberg, Horstmann, Hill, et al. reports on a genome-wide association study in Africans on association to the susceptibility of tuberculosis. The major finding is the identification of a susceptibility locus in a gene-poor region on chromosome 18q11.2 centered on SNP rs4331426.

My colleague Chao-Qiang Lai used Jonathan Pritchard's Haplotter data to discern that a comparison of YRI to CEU with Fst shows that this SNP, centered within a window of 151 SNPs, is within a group of variants (n=151) where 98% of the SNPs have Fst values greater than 95% of all SNPs. This is an indication that rs4331426 is under selection. With G as the minor allele and a minor allele frequency (MAF) in CEU of 0.025 and a MAF in YRI of 0.508, this difference in allele frequencies is noteworthy. In two Asian populations, MAFs are 0.03-0.04. Not surprisingly, we do not detect significant Fst between CEU and either of these two populations.

This is an important example, of which there is a growing body, in which genetic variation under selective pressure and disease phenotype(s) are linked. As diet constitutes a key aspect of the environment, we feel that there will be interesting findings at the intersection of selective pressure and metabolic-based disease.

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