rs12654264

This is a intron 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

Kathiresan S et al. “Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.” Nature Genetics 40(2):189-197 (2008)
Allele T
OR 0.10
p 1.0e-20
N 2,758
Large GWAS
European
Kim YJ et al. “Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.” Nature Genetics 43(10):990-5 (2011)
Allele T
OR 2.71
p 1.0e-20
N 12,545
Large GWAS
East Asian
Li D et al. “Progressive effects of single-nucleotide polymorphisms on 16 phenotypic traits based on longitudinal data.” Genes & Genomics 42(4):393-403 (2020)
Allele T
OR 2.63
p 1.0e-9
N 6,840
Large GWAS
East Asian

triglycerides in small LDL measurement

Karjalainen MK et al. “Genome-wide characterization of circulating metabolic biomarkers.” Nature 628(8006):130-138 (2024)
Allele A
OR 0.04
p 2.0e-19
N 136,016
Large GWAS
multi-ancestry

triglycerides in medium LDL measurement

Karjalainen MK et al. “Genome-wide characterization of circulating metabolic biomarkers.” Nature 628(8006):130-138 (2024)
Allele A
OR 0.04
p 1.0e-18
N 136,016
Large GWAS
multi-ancestry

esterified cholesterol measurement, blood VLDL cholesterol amount

Karjalainen MK et al. “Genome-wide characterization of circulating metabolic biomarkers.” Nature 628(8006):130-138 (2024)
Allele A
OR 0.03
p 5.0e-11
N 136,016
Large GWAS
multi-ancestry
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ClinVar annotation

Association
1 submitter1 publication

Low density lipoprotein cholesterol level quantitative trait locus 3 (LDLCQ3)

View on ClinVar →
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Research that mentions this SNP (1)

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Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study
AssociationN=5,576Logan Dumitrescu et al.(2012)· Human Genetics

This study investigated gene-environment interactions between 23 GWAS-identified lipid-associated SNPs and serum vitamins A and E in the National Health and Nutrition Examination Surveys (NHANES), including 5,576 participants across three racial/ethnic groups. Nine significant interactions were identified, with the most significant being APOB rs693×vitamin E associated with LDL-C in Mexican Americans (p=8.94×10⁻⁷). These nine interactions explained only 0.35-1.28% of variation in lipid traits, suggesting that gene-environment interactions account for modest proportions of the missing heritability in lipid metabolism.

Traits studied:HDL-C (High-Density Lipoprotein Cholesterol)LDL-C (Low-Density Lipoprotein Cholesterol)Triglycerides
PubMedDOIMetascience Observatory

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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