Association between Genetically Proxied Inhibition of HMG-CoA Reductase and Age at Onset of Huntington's Disease

Background: Previous studies have found that statins may play a potential role in the age at onset (AAO) of Huntington's disease (HD). We performed this Mendelian randomization (MR) study to assess the association between genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein (LDL) cholesterol with age at onset of HD. Methods: Single-nucleotide polymorphisms (SNPs) in HMG-CoA reductase associated with LDL cholesterol in a genome-wide association study (GWAS) analysis were used. The summary data of residual AAO of HD were obtained from a GWAS meta-analysis (n = 9064 HD patients). MR estimates representing lifelong inhibition of drug targets were generated using random-effects inverse-variance weighted analysis. Results: Genetically proxied plasma LDL cholesterol (beta = 0.039, 95% CI = -0.454 to 0.531) and HMG-CoA reductase inhibition equivalent to a 1 mmol/L (38.7 mg/dL) reduction in LDL cholesterol (beta = -2.228, 95% CI = -4.830 to 0.374) were not associated with age at onset of HD. Conclusion: The plasma LDL cholesterol levels and the reduction of plasma LDL cholesterol levels by the inhibition of HMG-CoA reductase (i.e., statins) were not associated with the age of HD onset.

Automated summary

This Mendelian randomization (MR) study aimed to assess the association between genetically proxied cholesterol and the age at onset of Huntington's disease (HD). The results showed that plasma cholesterol levels and HMG-CoA reductase inhibition were not associated with the age at onset of HD.