Genome-wide "pleiotropy scan" identifies XXXX region as a novel @entity788 susceptibility locus.

@entity1 @entity788 @entity6 @entity5 @entity72833 @entity5448 @entity165 @entity1851
In genome-wide association (GWA) studies, hundreds of thousands of single-nucleotide polymorphisms (SNP) are tested for association with a disease trait. Typically, GWA studies give equal consideration to all SNPs tested, regardless of existing knowledge of an SNP's functionality or biological plausibility of association. Because many tests are conducted, very low statistical significance thresholds (P < 5   10(-8)) are required to identify true associations with confidence. By restricting GWA analyses to SNPs with enhanced prior probabilities of association, we can reduce the number of tests conducted and relax the required significance threshold, increasing power to detect association. In this analysis of existing GWA data on @entity788 cases (n = 1,736) and controls (n = 1,802) of European descent (the PanScan study), we conduct a GWA scan restricted to SNPs that have been reported to associate with @entity1 phenotypes in previous GWA studies (with P < 5   10(-8)). Using this method, we drastically reduce the number of tests conducted (from ~550,000 to 1,087) and test only SNPs that are known to be (or tag) variants that influence @entity1 biological processes. Of the 1,087 SNPs tested, the strongest association observed was for @entity5448 SNP @entity72833 (P = 3   10(-5); P(Bonferroni) = 0.03), an SNP known to associate with circulating @entity1851 . This association was replicated in an independent sample of 1,094 cases and 1,165 controls (P = 0.02), producing a highly significant association in the combined data sets (P = 2   10(-6); P(Bonferroni) = 0.002). The @entity5448 region also harbors variants that influence several @entity1 traits, including maturity-onset @entity6 , low-density lipoprotein @entity165 , and N-glycan levels. This novel "pleiotropy scan" method may be useful for identifying susceptibility loci for other @entity5 phenotypes.
