Fig. 6 | Nature Communications

Fig. 6

From: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Fig. 6

Rare variant non-coding burden analyses. A schematic of rare variant association results from (1) aggregating rare variants in adult liver enhancers or promoters and strong DHS (P < 10−10) within 3 kb sliding windows, and (2) aggregating rare variants in liver enhancers grouped to LPA via the “By expression” in silico prediction method. In the top two panels, each red diamond represents the meta-analyzed mixed-model SKAT P-value with Lp(a)-C of rare (MAF < 1%), non-coding variants overlapping liver enhancer or promoter annotations in strong DHS (P(DHS) < 1e-10) grouped in a 3 kb window, before adjusting for KIV2-CN (top, “Original”) and after adjusting for KIV2-CN (bottom, “Conditioned on KIV2-CN”). The horizontal red lines denote the genome-wide Bonferroni significance threshold given the number of unique windows analyzed. The horizontal gray lines denote the Bonferroni significance threshold within this 1MB region around LPA. The regions incorporated into the “By Expression” grouping to LPA are shown in aqua, along with the respective associations of rare non-coding variants in these regions before and after conditioning on KIV2-CN. Annotated adult liver enhancers (green bars) and promoters (red bars) overlapping strong DHS are included above protein-coding genes from Ensembl. DHS DNAse hypersensitivity sites, Lp(a)-C lipoprotein(a) cholesterol, MAF minor allele frequency, SKAT Sequence Kernal Association Test