{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:17:37Z","timestamp":1771463857855,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Previous studies have found that statins may play a potential role in the age at onset (AAO) of Huntington\u2019s 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 (\u03b2 = 0.039, 95% CI = \u22120.454 to 0.531) and HMG-CoA reductase inhibition equivalent to a 1 mmol\/L (38.7 mg\/dL) reduction in LDL cholesterol (\u03b2 = \u22122.228, 95% CI = \u22124.830 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.<\/jats:p>","DOI":"10.3390\/brainsci12111551","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:27:34Z","timestamp":1668565654000},"page":"1551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association between Genetically Proxied Inhibition of HMG-CoA Reductase and Age at Onset of Huntington\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Yahui","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-0254","authenticated-orcid":false,"given":"Xusheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1001\/archneur.1993.00540110037003","article-title":"Molecular genetics of Huntington\u2019s disease","volume":"50","author":"Gusella","year":"1993","journal-title":"Arch. 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