Ischemic Heart Disease (IHD) is a leading cause of morbidity and mortality worldwide. Hypercholesterolaemia, a metabolic syndrome distinguished by elevated cholesterol levels, is positively correlated with IHD, yet the precise causal relationship between these two health conditions remains to be clearly defined.
We conducted a two-sample MR analysis using genetic variants associated with hypercholesterolemia and IHD. Various statistical techniques including MR-Egger, Weighted Median, Inverse Variance Weighted (IVW), Simple Mode, and Weighted Mode were employed. We also performed sensitivity analyses to assess pleiotropy, heterogeneity, and influence of individual SNPs. Furthermore, genetic co-localization analysis was performed to identify shared genes between hypercholesterolemia and IHD.
Our MR study illuminated a bidirectional causal relationship between hypercholesterolaemia and ischaemic heart disease. Utilising the IVW with multiplicative random effects, upon considering IHD as the outcome, we identified an OR of 2.27 (95% CI: 1.91–2.70,
bidirectional MR studies reveal genetic evidence of a potential causal link between hypercholesterolaemia and IHD. Notably, these findings also lend credence to the less traditional hypothesis that IHD may instigate hypercholesterolaemia episodes. Moreover, co-localisation analyses intimate the presence of shared genetic causal variants, paving the way for the development of new therapeutic strategies.