Fig. 4: Conditional analysis of coding rare-variants from the same gene and a near-by gene.

Non-coding rare variant sets significantly associated with TC and TG after the conditional analysis on known variants are shown with additional adjustment on rare-coding variants. The additional adjustment for rare-coding variants were carried out for the same gene of the aggregate set and for certain gene aggregates (SPC24) the conditional analysis was carried out with a nearby Mendelian gene. After adjusting for rare-coding variants and known variants, EHD3 signal drops minimally, whereas signal from PCSK9 (promoter-DHS, enhancer-DHS), LDLR-loci (enhancer-DHS, SPC24 enhancer-DHS) enhances significantly. APOB1, SPC24 (enhancer-CAGE), HBB and APOE signal drops after the conditional analysis on rare-coding variants. The different colored dots on the plot represents the conditional STAAR-O p-values when adjusting for known variants (Set1) and rare-coding variants of the same or near-by gene. The p-values were calculated from two-sided aggregate testing preformed using STAAR gene-centric model, where the model was adjusted for all the covariates; see Methods. STAAR variant-Set Test for Association using annotation information, TC total cholesterol, TG triglycerides, CAGE cap analysis of gene expression, DHS DNase hypersensitivity.