Fig. 2: Transcriptome-wide association study in human aortic valve and Mendelian randomization identify novel candidate causal genes at genome-wide significant loci.
a, d, g LocusCompare plots at the PRRX1, ATP13A3, and TWIST1 loci. P for calcific aortic valve stenosis was obtained from the inverse-variance weighted fixed-effect GWAS meta-analysis. P for valve eQTL was obtained from the nominal association between genotype and normalized gene expression. b, e, h Boxplots showing normalized gene expression in human aortic valves according to the genotype at the lead SNP at the PRRX1, ATP13A3, and TWIST1 loci. The center mark in the box represents the median, the bounds of the box represent the 25th and 75th percentiles and the whiskers are the most extreme data point, which is no more than 1.5 times the interquartile range. P GWAS was obtained from the inverse-variance weighted fixed-effect GWAS meta-analysis. P eQTL was obtained from the nominal association between genotype and normalized gene expression. The allele in red is the risk allele. c, f, i Scatterplot representing the effect of each SNP selected in the instrument for the Mendelian randomization (MR) analysis on gene expression in human aortic valves (n = 484) and risk of calcific aortic valve stenosis (n = 14,819 cases and 927,044 controls) at the PRRX1, ATP13A3, and TWIST1 loci. Data are presented as the effect and 95% confidence interval (+/−1.96*standard error). Red line: inverse-variant weighted (IVW) MR; Dotted red lines: 95% confidence interval for IVW MR; Green line: Weighted median MR; Pink line: Egger MR.
