What you carry at this position in your DNA and what research says about it.
Heart Disease and Cholesterol: 10/10 evidence, 50 publications.
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Sample genotype (not yours): G/G
Typical Cholesterol and Heart Disease Risk
Standard baseline levels of cholesterol and typical cardiovascular risk characterize this genetic profile.
What this genotype means: Typical baseline LDL cholesterol levels; Standard risk of coronary artery disease; Standard response to statin therapy.
Sample genotype (not yours): G/T
Lower Cholesterol and Reduced Heart Risk
Presence of a single protective T allele is linked to lower LDL cholesterol levels and a reduced risk of heart disease.
What this genotype means: Lower circulating LDL cholesterol; Reduced risk of coronary artery disease; Slightly enhanced response to statin therapy.
Sample genotype (not yours): T/T
Lowest Cholesterol and Lowest Heart Risk
Presence of two protective T alleles is linked to the lowest average LDL cholesterol levels and a significantly reduced risk of heart disease.
What this genotype means: Lowest average LDL cholesterol levels; Significantly reduced risk of coronary artery disease; Enhanced response to statin therapy.
Gene function and biological role
Gene Function: The CELSR2 gene is part of a highly studied genetic cluster on chromosome 1p13 that plays a critical role in regulating blood lipid levels [1]. While CELSR2 itself encodes a receptor protein involved in cell-to-cell signaling, its genomic region acts as a powerful regulatory hub [2]. Specifically, variants within this region influence the expression of the neighboring SORT1 gene in liver cells [2]. This liver-specific regulation directly controls how low-density lipoprotein (LDL) cholesterol is cleared from the bloodstream [2]. Consequently, this gene cluster is one of the most significant genetic determinants of cardiovascular health in the human genome [1].
Variant Impact: The rs12740374 variant is a noncoding genetic change located in the 3 prime untranslated region of the CELSR2 gene [2]. Rather than altering a protein structure directly, this change creates a novel binding site for transcription factors in liver tissue [2]. This newly created site significantly boosts the activity of the nearby SORT1 gene, leading to increased production of sortilin proteins [2]. Sortilin acts as a receptor that enhances the liver's ability to clear LDL cholesterol from circulation and reduces the secretion of other lipid particles [2]. Because of this direct biological mechanism, this single nucleotide change has a profound impact on lifetime cholesterol levels and heart attack risk [3].
Key Insight: A single letter change in a noncoding region of DNA can alter heart attack risk by up to forty percent by acting as a genetic volume dial in the liver.
Location: CELSR2. Chromosome 1 · 1p13.3 · 109.3 Mb
Estimated prevalence by population
Global 60.7%; European 60.7%; African 56.3%; East Asian 88.0%; South Asian 57.2%; Americas 62.4%; Ashkenazi 69.1%; Finnish 60.7%; Middle Eastern 80.0%; Amish 45.2%.
Estimated GG genotype frequency.
Global 34.3%; European 34.4%; African 37.4%; East Asian 11.6%; South Asian 36.9%; Americas 33.2%; Ashkenazi 28.1%; Finnish 34.4%; Middle Eastern 18.9%; Amish 44.1%.
Estimated GT genotype frequency.
Global 5.0%; European 4.9%; African 6.2%; East Asian 0.4%; South Asian 6.0%; Americas 4.4%; Ashkenazi 2.9%; Finnish 4.9%; Middle Eastern 1.1%; Amish 10.8%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 19060906. Typical Levels.
Heart Disease
Coronary Artery Disease. Evidence: 10/10. Source: PMID 29212778. Typical Risk.
Heart Attack. Evidence: 10/10. Source: PMID 33532862. Typical Risk.
Vascular Health & Aneurysm
Abdominal Aortic Aneurysm. Evidence: 8/10. Source: PMID 34469433. Typical Risk.
Pharmacogenomics
Lipid-Lowering Drug Response
Statin Response. Evidence: 3/10. Source: PMID 29356453. Typical Response.
Lifestyle, Fitness & Aging
Height & Body Size
Height. Evidence: 10/10. Source: PMID 30595370. Typical Height.
Showing effects for G/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 19060906. Lower Levels.
Coronary Artery Disease. Evidence: 10/10. Source: PMID 29212778. Lower Risk.
Heart Attack. Evidence: 10/10. Source: PMID 33532862. Lower Risk.
Abdominal Aortic Aneurysm. Evidence: 8/10. Source: PMID 34469433. Lower Risk.
Statin Response. Evidence: 3/10. Source: PMID 29356453. ~1.3% Higher Response.
Height. Evidence: 10/10. Source: PMID 30595370. Slightly Taller.
Showing effects for T/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 19060906. Lowest Levels.
Coronary Artery Disease. Evidence: 10/10. Source: PMID 29212778. Lowest Risk.
Heart Attack. Evidence: 10/10. Source: PMID 33532862. Lowest Risk.
Abdominal Aortic Aneurysm. Evidence: 8/10. Source: PMID 34469433. Lowest Risk.
Statin Response. Evidence: 3/10. Source: PMID 29356453. ~2.6% Higher Response.
Height. Evidence: 10/10. Source: PMID 30595370. Taller.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Two copies of the major ancestral G allele establish a typical baseline for blood lipid levels. This profile is associated with typical baseline levels of low-density lipoprotein (LDL) cholesterol and overall cardiovascular risk [1]. Because this genotype lacks the protective T allele, it does not benefit from the enhanced liver-specific clearance of LDL particles seen in carriers [2]. Large-scale genome-wide association studies show that individuals with this baseline profile have standard rates of coronary artery disease and myocardial infarction compared to the general population [3]. Standard cardiovascular health guidelines, including maintaining a balanced diet and regular exercise, remain the primary tools for managing lipid levels. If cholesterol levels become elevated, standard therapeutic interventions like statins are highly effective, though carriers of the protective allele may experience a slightly more pronounced response [4].
Typical baseline LDL cholesterol levels; Standard risk of coronary artery disease; Standard response to statin therapy.
Sample genotype: GT (Heterozygous)
One copy of the protective minor T allele alters liver gene expression to favor cardiovascular health. This single copy is sufficient to create a functional binding site in the liver, boosting the expression of the SORT1 gene [1]. As a result, the liver produces more sortilin, which actively pulls LDL cholesterol out of the bloodstream and lowers circulating lipid levels [1]. Clinical studies demonstrate that carriers of this protective allele have significantly lower LDL and total cholesterol levels compared to those with the typical G/G genotype [2]. This natural reduction in circulating lipids translates directly into a lower lifetime risk of coronary artery disease and heart attacks [3]. Additionally, pharmacogenomic research suggests that individuals with this profile may experience slightly enhanced benefits from statin medications, making lipid-lowering therapies highly effective if they are ever needed [4].
Lower circulating LDL cholesterol; Reduced risk of coronary artery disease; Slightly enhanced response to statin therapy.
Sample genotype: TT (Homozygous)
Double copies of the protective minor T allele maximize the liver's natural capacity to clear cholesterol. This double-copy profile maximizes the liver-specific expression of the SORT1 gene, leading to the highest levels of sortilin production [1]. Consequently, the liver is exceptionally efficient at clearing LDL cholesterol from the bloodstream and reducing the secretion of very-low-density lipoproteins [1]. Large-scale genomic cohorts show that individuals with this genotype have the lowest average LDL and total cholesterol levels among all groups [2]. This biological advantage translates into a highly significant reduction in the lifetime risk of developing coronary artery disease or experiencing a myocardial infarction [3]. Furthermore, clinical trials have noted that this genotype is associated with an increased effectiveness of statin therapies, providing an extra layer of cardiovascular protection if intervention is required [4].
Lowest average LDL cholesterol levels; Significantly reduced risk of coronary artery disease; Enhanced response to statin therapy.
Variants with shared genetic architecture
rs629301 · CELSR2 Gene · Chr 1 · Cholesterol and Heart Risk
rs660240 · CELSR2 Gene · Chr 1 · LDL Cholesterol Levels
rs7528419 · CELSR2 Gene · Chr 1 · Heart Disease Risk
Common variants at 30 loci contribute to polygenic dyslipidemia.
From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus.
Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.
Content updated August 2026.
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