Figure 2

OPEN successfully prioritizes causal genes for complex traits. (A) Receiver operating characteristic (ROC) curves for prioritization of 'likely positive' genes for LDL-cholesterol. (B) OPEN effectively prioritizes likely positives for low-density lipoprotein (LDL)-cholesterol within GWA loci. A histogram shows the distribution of the number of genes prioritized by random chance over 10,000 independent simulations, with arrow indicating the number prioritized by OPEN (P < 0.0001). (C) OPEN successfully prioritizes the statin target HMGCR at the 5q13.3 locus (left). A heatmap depicts the six genes at the LDL-associated 5q13.3 locus, with the first four columns indicating which genes are near the index variant, and which have been annotated with prior evidence via the Gene Ontology (GO), Mouse Phenotype Database (MPD) or through the Online Mendelian Inheritance in Man (OMIM) database. The final column depicts the OPEN score, with color scheme from beige to dark purple indicating increasing magnitude of the log odds for disease association provided by OPEN. At the 2p15 LDL-associated locus (right), OPEN ranks the un-annotated EHBP1 gene highest. (D) Area under the ROC curve (AUROC) values for cardiac (left) and non-cardiac phenotypes (right). EKG, electrocardiogram; HDL, high-density lipoprotein.