Background: Despite the widespread use of statins, newer lipid-lowering drugs have been emerging. It remains unclear how the long-term use of novel lipid-lowering drugs affects the occurrence of cancers and age-related diseases.
Methods: A drug-target Mendelian randomization study was performed. Genetic variants of nine lipid-lowering drug-target genes (, and ) were extracted as exposures from the summary data of Global Lipids Genetics Consortium Genome-Wide Association Studies (GWAS). GWAS summary data of cancers and noncancerous diseases were used as outcomes. The inverse-variance weighted method was applied as the main statistical approach. Sensitivity tests were conducted to evaluate the robustness, pleiotropy, and heterogeneity of the results.
Results: In addition to marked effects on decreased risks of atherosclerotic cardiovascular diseases, genetically proxied lipid-lowering variants of , , , , and were associated with longer human lifespans (). Lipid-lowering variants of and were associated with reduced risks of colorectal cancer, and was also associated with lower risks of gastric cancer (). Lipid-lowering variants were associated with decreased risks of hypertension, type 2 diabetes, nonalcoholic fatty liver disease, and bladder cancer (). Lipid-lowering variants of and were associated with decreased risks of osteoporosis (). Lipid-lowering variants were associated with a decreased risk of thyroid cancer ().
Conclusions: Our study provides genetic evidence that newer nonstatin lipid-lowering agents have causal effects on decreased risks of several common cancers and cardiometabolic diseases. These data provide genetic insights into the potential benefits of newer nonstatin therapies.
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| http://dx.doi.org/10.18632/aging.205347 | DOI Listing |
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