HaploReg: Examples

Single locus. In a study of tooth development by Pillas et al., an association was reported between the intergenic SNP rs6504340 and dental occlusion. In the first tab, "Build Query", enter rs6504340. In the second tab, "Set Options", set the LD threshold to 1.0. Then click "Submit Query", below the options. Note that there are five variants reported: the original query SNP, an indel (absent from YRI), and three other SNPs. One of these SNPs is a synonymous coding change in HOXB1, and the query SNP and other two linked SNPs are intergenic. One lies in a conserved element by both the GERP and SiPhy algorithms: rs8073963. Click on the name of this SNP, and a detail box will page will open. Note that besides being an enhancer in K562 (reported on the main page), the chromatin state in eight other cell types is reported: polycomb-repressed in H1, HepG2, and Huvec, and heterochromatic in GM12878, HMEC, HSMM, NHEK, and NHLF. The locus is found to be DNAse-sensitive by two different ENCODE production groups, although in different cells. Hits to two literature PWMs for Foxo are detected. Because the LOD(alt)-LOD(ref) is negative, the affinity in the reference sequence is higher. In both cases, the SNP affects a match to the "C" at the end of the PWM (which matches on the minus strand; the plus strand reference allele is G.)

Multiple loci. Ernst et al. report an enrichment among the lupus GWAS SNPs from Han et al. In the first tab, "Build Query", select "Systemic lupus erythematosus (Han et al., 2009), 18 SNPs" from the GWAS drop-down menu. In the second tab, "Set Options", select an LD threshold of 1.0 and set the 1000G population to ASN (the study's subjects were Han Chinese). Now click "Submit Query." Note that the SNPs appear in separate tables with their LD blocks (the second is at the HLA locus.) Also note that the enhancer enrichment analysis reports an enrichment for enhancers in HSMM and GM12878. (This enrichment is based on the query SNPs and is indepenedent of the population or LD threshold.) Now select "Systemic lupus erythematosus (8 studies combined), 62 SNPs" in the first tab and select an LD threshold of "NA" in the second tab, and click "Submit Query." Note that all variants appear in the same table.