Significant associations may also be due to the variant being in linkage disequilibrium with a functional variant. While linkage disequilibrium (LD) decreases with increasing distance between markers, studies of some genes have shown that LD may be quite high past 100,000 nucleotides (Collins et al., 1999, Reich et al., 2001). In this study, if an annotated gene was found within 100,000 nucleotides of a variant, the gene’s location relative to that variant is indicated. Mammalian conservation was determined using the “Vertebrate Multiz Alignment & PhastCons Conservation (28 species)” and the “Evolutionary and Sequence Pattern Extraction through Reduced Representation” (ESPERR) (King et al., 2005) to evaluate predicted regulatory potential as implemented in the UCSC Genome Browser (March 2006 assembly, http://gemome.ucsc.edu/). The “Transcription Element Search System” (TESS) was used to scan sequences for predicted transcription factor binding sites (Schug and Overton, 1977).
