{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:08:28Z","timestamp":1779934108873,"version":"3.53.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The causal relationship between familial hypercholesterolemia (FH) and various vitamin deficiencies has not yet been elucidated. Therefore, this study investigated the cause-and-effect relationship between FH and the risk of multiple vitamin deficiencies in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mendelian randomization (MR) analysis was performed by extracting six datasets for FH, FH with ischemic heart disease (IHD), and vitamin deficiency (vitamin A, thiamine, other B-group vitamins, and vitamin D) from the FinnGen study, covering a total of 329,115; 316,290; 354,932; 354,949; 355,411 and 355,238 individuals, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FH was suggestively associated with higher odds of thiamine deficiency [inverse variance weighted odds ratio (OR<jats:sub>IVW<\/jats:sub>) 95% confidence interval (CI): 1.62 (1.03, 2.55), <jats:italic>P<\/jats:italic> = 0.036] and vitamin D deficiencies [OR<jats:sub>IVW<\/jats:sub> CI: 1.35 (1.04, 1.75), <jats:italic>P<\/jats:italic> = 0.024], low-density lipoprotein receptor (<jats:italic>LDLR<\/jats:italic>) rs112898275 variant, rs11591147 and rs499883 in proprotein convertase subtilisin\/kexin 9 (<jats:italic>PCSK9<\/jats:italic>), rs9644862 in cyclin-dependent kinase inhibitor 2 B antisense RNA1 (<jats:italic>CDKN2B-AS1<\/jats:italic>), and rs142834163 in dedicator of cytokinesis 6 (<jats:italic>DOCK6<\/jats:italic>) and rs115478735 in ABO blood group (<jats:italic>ABO<\/jats:italic>) strongly influenced the risk of thiamine deficiency, while the rs7412 variant in apolipoprotein E (<jats:italic>APOE<\/jats:italic>) mostly influenced the risk of vitamin D deficiency. FH with IHD was suggestively associated with higher odds of vitamin D deficiency (OR<jats:sub>IVW,<\/jats:sub> weighted median [WM][95%CI]: 1.31 [1.05, 1.64]; 1.47 [1.10, 1.97]) (<jats:italic>P<\/jats:italic> = 0.018; 0.010) without any single significant SNPs observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FH was positively associated with increased risks of thiamine and vitamin D deficiencies, revealing a prospective and unfortunate complication of FH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1401260","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:28:10Z","timestamp":1729571290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal relationships of familial hypercholesterolemia with the risk of multiple vitamin deficiencies: a Mendelian randomization 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