rs3846663

This is a upstream gene variant variant in the HMGCR gene.

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GWAS Catalog Trait Associations (4)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

low density lipoprotein cholesterol measurement

Petty LE et al. “Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.” Nature Communications 16(1):3438 (2025)
Allele T
OR 0.07
p 3.0e-33
N 60,405
Large GWAS
Hispanic or Latin American
Kulminski AM et al. “Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75(10):1811-1819 (2020)
Allele T
OR 2.51
p 2.0e-15
N 29,902
Large GWAS
European
Kathiresan S et al. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nature Genetics 41(1):56-65 (2009)
Allele T
OR 0.07
p 8.0e-12
N 19,840
Large GWAS
European

total cholesterol measurement

Kulminski AM et al. “Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75(10):1811-1819 (2020)
Allele T
OR 2.79
p 2.0e-16
N 29,902
Large GWAS
European

fatty acid amount

Richardson TG et al. “Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation.” Plos Biology 20(2):e3001547 (2022)
Allele C
OR 0.03
p 3.0e-14
N 115,006
Large GWAS
European

non-high density lipoprotein cholesterol measurement

Graham SE et al. “The power of genetic diversity in genome-wide association studies of lipids.” Nature 600(7890):675-679 (2021)
Allele T
OR 0.05
p 3.0e-13
N 40,963
Large GWAS
South Asian

About HMGCR

HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

View all HMGCR variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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