Comparison of total expression levels of regions annotated to intergenic lncRNAs, exons, introns, and intergenic regions.

<p>The horizontal axes in the panels show bins of fluorescence signals from the genotyping data, summed for both alleles to give a measure for total expression. The average expression levels of annotated transcripts were 4900 fluorescence units in exons, 2100 in introns, 590 in intergenic regions, compared to 3300 in the intergenic lncRNA regions that were used in the ASE analysis. The vertical axes show the number of observations in each bin.</p

Illustration of a region with a SNP from genome wide association studies (GWAS) which is associated with ASE of lncRNAs.

<p>The tracks are from top to bottom in each panel: Horizontal red bars represent lncRNA transcript windows (with genomic coordinates) used for determination of ASE levels; grey lines show p-values for the association of GWAS SNPs with ASE levels in the transcript window; a grey line overlayed with a red dotted line indicates that a <i>cis</i>-rSNP overlaps with the reported SNP in the GWAS catalog; red vertical lines are median ASE-levels for each SNP.</p

SNPs associated with allele-specific expression of lncRNA windows with published trait- or disease-associations from genome-wide association studies.

1<p>The distance to the lncRNA region is 0 if the SNP is located within the region and the smallest distance otherwise,</p>2<p>Slope is given in absolute numbers,</p>3<p>Listed are all cis-rSNPs that are also found in the GWAS catalog together with the associated lncRNA,</p>4<p>The trait is taken from the GWAS catalog,</p>5<p>Within 2.5 kb,</p>6<p>rs6663565 as proxy,</p>7<p>rs2303393 as proxy,</p>8<p>rs6922111 as proxy,</p>9<p>rs7739434 as proxy,</p>10<p>rs13214831 as proxy,</p>11<p>rs1153862 as proxy,</p>12<p>rs12442557 as proxy.</p

Manhattan plot.

<p>Manhattan plot with the p-values from ASE association tests between SNPs and lncRNAs on the vertical axis and the genomic lncRNA regions analysed in the study on the horizontal axis. The p-value cut-off of 10⁻⁶ is shown as a grey line.</p

Co-expressed lncRNA regions and protein-coding genes.

1<p>All 52 significantly co-expressed lncRNA and protein coding genes with a lncRNA associated <i>cis</i>-rSNP are listed.</p>2<p>Multiple testing correction using FDR of 10%,</p>3<p>The p-value cut-off for significant ASE is 10⁻⁶,</p>4<p>ASE p-value for a Refseq gene is shown for all regions that are co-expressed with a lncRNA and have an overlapping ASE analysis window, NA otherwise.</p

Overlap of significantly associated rSNPs identified by ASE and GTE.

<p>The percentage of overlapping rSNPs detected by allele-specific expression (ASE) and genotype expression (GTE) analysis is plotted for varying numbers of samples. The top 9536 SNPs from the GTE analysis are compared with the top 38203 SNPs from the ASE analysis, which corresponds to a Bonferroni threshold of p = 0.05 for a GTE sample size of 395 and an ASE sample size of 188. The p-value cut-offs were adapted so that the same SNP top-list sizes were obtained at all sample sizes for both GTE (p-value of 1.17E-7, 1.06E-4, 1.93E-3, 6.12E-3 for n = 395, n = 188, n = 95, and n = 50 respectively) and ASE (p-value of 8.06E-8, 9.35E-5, 4.90E-3 for n = 188, n = 95, and n = 50 respectively). The vertical axes show the percentage of SNPs in the top-lists detected by both GTE and ASE analysis and the horizontal axes show the number of samples analyzed using GTE and ASE, respectively. The percentage overlap is calculated by dividing the number of overlaps with the number of top SNPs in the GTE analysis. In (A), each line shows the effect on the number of overlapping SNPs detected by ASE analysis of a specific sample size when the sample size in GTE analysis was increased. In (B), each line shows the effect on the number of overlapping rSNPs detected by GTE analysis of a specific sample size when the samples size in ASE analysis is increased.</p

The ability of ASE and GTE analysis to detect significantly associated rSNPs at different MAF.

<p>Fractions of rSNPs are shown for different minor allele frequencies (MAF) with significant association signals according to a Bonferroni-corrected p-value of 0.05. Each data point underlying the curves represents the fraction of significant associations within a 1% MAF bin. Sliding 5% MAF window averages are plotted for different sample sizes analyzed by ASE and GTE. Both methods detect a lower fraction of low frequency rSNPs, compared to the fraction of all the SNPs at the same frequency (black line). The ASE method detects a higher fraction of the SNPs (solid lines) with a MAF <15% than GTE (dashed lines) regardless of sample size except for the largest GTE sample set.</p