These results suggest that the extended lifespan caused by statins might be achieved through upregulating LDLR more than HMGCR, as LDLR showed more convincing genetic evidence of causally affecting human longevity than HMGCR. In addition, the mediation analysis further suggested that genetic mimicry of LDLR enhancement may extend the human lifespan by reducing the risks of major CHD events, which is also consistent with the results from clinical trials. This evidence concerns the gene HMGCR and coronary artery disorder.