What you carry at this position in your DNA and what research says about it.
HDL Cholesterol Levels: 10/10 evidence, 24 publications.
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Sample genotype (not yours): A/A
Typical HDL Cholesterol and Lipid Levels
This genotype is associated with typical levels of HDL cholesterol and standard cardiovascular risk. It is the most common genetic profile globally.
What this genotype means: Typical endothelial lipase activity; Standard baseline HDL cholesterol levels; Typical risk for depressive symptoms.
Sample genotype (not yours): A/G
Elevated HDL Cholesterol and Typical Heart Risk
This genotype raises HDL cholesterol levels but does not lower the risk of heart disease. It is also associated with a higher likelihood of experiencing depressive symptoms.
What this genotype means: Reduced endothelial lipase activity; Elevated circulating HDL cholesterol levels; Slightly increased risk for depressive symptoms.
Sample genotype (not yours): G/G
Significantly Elevated HDL and Typical Heart Risk
This rare genotype significantly elevates HDL cholesterol levels due to reduced lipase activity. However, it does not provide protection against heart disease and is linked to depressive symptoms.
What this genotype means: Markedly reduced endothelial lipase activity; Highly elevated circulating HDL cholesterol levels; Increased risk for depressive symptoms.
Gene function and biological role
Gene Function: The LIPG gene encodes endothelial lipase, an enzyme that plays a critical role in lipoprotein metabolism by hydrolyzing phospholipids within high-density lipoprotein particles [1]. This enzymatic breakdown directly regulates how quickly HDL is cleared from the bloodstream [1]. When endothelial lipase activity is high, HDL particles are rapidly cleared, resulting in lower circulating HDL cholesterol levels [1]. Conversely, reduced activity of this enzyme leads to an accumulation of HDL particles, which elevates measured blood levels of HDL cholesterol [2].
Variant Impact: The rs77960347 variant is a missense mutation in the LIPG gene that replaces the amino acid asparagine with serine at position 396 [1]. This specific amino acid substitution impairs the enzymatic function of endothelial lipase, reducing its ability to break down HDL phospholipids [1]. Consequently, individuals carrying the variant allele have significantly elevated levels of circulating HDL cholesterol [1]. Interestingly, this variant was famously used in landmark genetic studies to demonstrate that genetically elevated HDL levels do not automatically translate to a reduced risk of heart disease [2].
Key Insight: This variant proved to scientists that raising HDL good cholesterol does not automatically protect against heart attacks, challenging decades of medical assumptions.
Location: LIPG. Chromosome 18 · 18q21.1 · 49.6 Mb
Estimated prevalence by population
Global 98.4%; European 97.6%; African 99.5%; East Asian 100.0%; South Asian 99.3%; Americas 98.2%; Ashkenazi 98.3%; Finnish 98.9%; Middle Eastern 96.0%; Amish 99.8%.
Estimated AA genotype frequency.
Global 1.6%; European 2.4%; African 0.5%; East Asian 0.0%; South Asian 0.7%; Americas 1.7%; Ashkenazi 1.7%; Finnish 1.1%; Middle Eastern 4.0%; Amish 0.2%.
Estimated AG genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern < 0.1%; Amish < 0.1%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
HDL Cholesterol. Evidence: 10/10. Source: PMID 24507774. Typical Levels.
Total Cholesterol. Evidence: 10/10. Source: PMID 30275531. Typical Levels.
Heart Disease
Heart Attack. Evidence: 8/10. Source: PMID 32203549. Typical Risk.
Neurology & Mental Health
Mood Disorders
Depressive Symptoms. Evidence: 8/10. Source: PMID 36764567. Typical Risk.
Showing effects for A/G genotype
HDL Cholesterol. Evidence: 10/10. Source: PMID 24507774. Elevated Levels.
Total Cholesterol. Evidence: 10/10. Source: PMID 30275531. Slightly Elevated.
Depressive Symptoms. Evidence: 8/10. Source: PMID 36764567. Increased Risk.
Showing effects for G/G genotype
HDL Cholesterol. Evidence: 10/10. Source: PMID 24507774. Highly Elevated.
Depressive Symptoms. Evidence: 8/10. Source: PMID 36764567. Higher Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Most individuals carry two copies of the common A allele, resulting in fully functional endothelial lipase enzymes [1]. This enzyme efficiently processes high-density lipoprotein particles, maintaining typical baseline levels of HDL cholesterol in the bloodstream [1]. Because this is the standard genetic baseline, there is no genetically driven elevation in HDL or total cholesterol from this locus [2]. Standard lifestyle factors like diet and exercise remain the primary drivers of lipid profiles for this group [2]. Additionally, this genotype is associated with a typical baseline risk for depressive symptoms and cognitive decline [3]. No special dietary or medical interventions are suggested based on this genetic profile.
Typical endothelial lipase activity; Standard baseline HDL cholesterol levels; Typical risk for depressive symptoms.
Sample genotype: AG (Heterozygous)
Carrying one copy of the G allele reduces the activity of endothelial lipase, leading to higher circulating levels of HDL cholesterol [1]. While HDL is traditionally labeled as good cholesterol, large-scale genetic studies using this variant show that this specific elevation does not lower heart attack risk [2]. The genetic profile also slightly increases total and LDL cholesterol levels [2]. Beyond cardiovascular markers, some clinical research has linked this variant to an increased risk of depressive symptoms and changes in brain white matter [3]. This suggests a complex role for endothelial lipase in both lipid regulation and neurological health [3]. Overall, the cardiovascular impact remains neutral despite the higher HDL numbers.
Reduced endothelial lipase activity; Elevated circulating HDL cholesterol levels; Slightly increased risk for depressive symptoms.
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele is extremely rare and leads to a pronounced reduction in endothelial lipase activity [1]. This functional deficit causes a substantial increase in circulating HDL cholesterol levels [1]. Despite the very high HDL levels, genetic evidence confirms that this does not translate to a reduced risk of coronary artery disease or myocardial infarction [2]. The genotype is also associated with slight elevations in total cholesterol and red cell distribution width [2]. Furthermore, studies on this variant suggest a potential increase in susceptibility to depressive symptoms and related neurological traits [3]. Because the cardiovascular benefits of high HDL are not realized here, maintaining standard cardiovascular health habits remains important.
Markedly reduced endothelial lipase activity; Highly elevated circulating HDL cholesterol levels; Increased risk for depressive symptoms.
Variants with shared genetic architecture
rs2156552 · LIPG Gene · Chr 18 · HDL Cholesterol Levels
rs4939883 · LIPG Gene · Chr 18 · HDL Cholesterol Levels
rs7241918 · LIPG Gene · Chr 18 · HDL Cholesterol Levels
Content updated August 2026.
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