What you carry at this position in your DNA and what research says about it.
Heart Disease Risk: 8/10 evidence, 15 publications.
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Sample genotype (not yours): G/G
Lower Heart Disease Risk and Favorable Lipids
A healthier cardiovascular profile is linked to the protective G/G combination. It is associated with lower blood pressure, higher HDL cholesterol, and lower triglycerides.
What this genotype means: Lower risk of coronary artery disease; Higher protective HDL cholesterol levels; Lower blood pressure and triglycerides.
Sample genotype (not yours): G/T
Slightly Elevated Heart Disease Risk
A slight increase in cardiovascular risk is associated with the G/T combination. It is linked to mildly higher triglycerides and blood pressure.
What this genotype means: Slightly higher risk of coronary artery disease; Mildly elevated triglycerides; Slightly lower HDL cholesterol.
Sample genotype (not yours): T/T
Elevated Heart Disease Risk and Higher Triglycerides
A higher risk of coronary artery disease is associated with the T/T combination. It is also linked to elevated triglycerides and blood pressure.
What this genotype means: Increased risk of coronary artery disease; Elevated triglycerides and lower HDL cholesterol; Higher systolic and diastolic blood pressure.
Gene function and biological role
Gene Function: The IRS1 gene encodes insulin receptor substrate 1, a key signaling protein that transmits signals from the insulin receptor to intracellular pathways. This protein plays a central role in regulating glucose metabolism, cell growth, and insulin sensitivity across various tissues [1]. Proper functioning of this pathway is essential for maintaining healthy blood sugar levels and lipid metabolism [2]. Disruptions or reduced expression of this gene are strongly linked to insulin resistance, type 2 diabetes, and cardiovascular complications [1] [2].
Variant Impact: Located downstream of the IRS1 gene, rs2972146 is an intergenic genetic change. It acts as a cis-expression quantitative trait locus, meaning it directly influences how much IRS1 protein is produced in adipose tissue [1]. The T allele is associated with decreased expression of IRS1, which impairs insulin signaling and alters lipid metabolism [1]. Consequently, this genetic change is robustly associated with altered blood lipid profiles, blood pressure, and cardiovascular risk [3].
Key Insight: Although this variant is located outside of the actual IRS1 gene, it acts as a remote control that directly reduces the gene's activity in fat tissue, driving systemic metabolic changes.
Location: IRS1. Chromosome 2 · 2q36.3 · 226.2 Mb
Estimated prevalence by population
Global 8.7%; European 13.1%; African 2.5%; East Asian 0.5%; South Asian 5.3%; Americas 6.1%; Ashkenazi 8.3%; Finnish 13.7%; Middle Eastern 20.7%; Amish 18.6%.
Estimated GG genotype frequency.
Global 38.3%; European 46.2%; African 26.4%; East Asian 13.5%; South Asian 35.4%; Americas 37.1%; Ashkenazi 41.0%; Finnish 46.7%; Middle Eastern 49.6%; Amish 49.0%.
Estimated GT genotype frequency.
Global 53.0%; European 40.8%; African 71.1%; East Asian 86.0%; South Asian 59.4%; Americas 56.8%; Ashkenazi 50.8%; Finnish 39.6%; Middle Eastern 29.6%; Amish 32.4%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Heart Disease
Heart Disease. Evidence: 8/10. Source: PMID 28714974. Lower Risk.
Lipids & Cholesterol
HDL Cholesterol. Evidence: 8/10. Source: PMID 20686565. Higher Levels.
Triglycerides. Evidence: 10/10. Source: PMID 20686565. Lowest Levels.
Hypertension
Blood Pressure. Evidence: 8/10. Source: PMID 27618447. Lowest Levels.
Showing effects for G/T genotype
Heart Disease. Evidence: 8/10. Source: PMID 28714974. Slightly Higher Risk.
HDL Cholesterol. Evidence: 8/10. Source: PMID 20686565. Slightly Lower Levels.
Triglycerides. Evidence: 10/10. Source: PMID 20686565. Slightly Higher Levels.
Blood Pressure. Evidence: 8/10. Source: PMID 27618447. Slightly Higher Levels.
Showing effects for T/T genotype
Heart Disease. Evidence: 8/10. Source: PMID 28714974. ~1.1x Higher Risk.
HDL Cholesterol. Evidence: 8/10. Source: PMID 20686565. Lowest Levels.
Triglycerides. Evidence: 10/10. Source: PMID 20686565. Highest Levels.
Blood Pressure. Evidence: 8/10. Source: PMID 27618447. Highest Levels.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Optimal metabolic and cardiovascular health is strongly associated with the G/G genotype. Studies show that the G allele promotes higher expression of the IRS1 gene in adipose tissue, enhancing insulin sensitivity [1]. As a result, higher levels of protective HDL cholesterol are commonly observed [2]. Circulating triglycerides and blood pressure also tend to remain lower, which collectively reduces the risk of developing coronary artery disease [1] [2]. Maintaining a balanced diet and regular exercise can further maximize these genetic cardiovascular advantages.
Lower risk of coronary artery disease; Higher protective HDL cholesterol levels; Lower blood pressure and triglycerides.
Sample genotype: GT (Heterozygous)
An intermediate metabolic profile is typical for those with the G/T genotype due to the presence of one risk allele and one protective allele. A single copy of the T allele is linked to slightly reduced expression of the IRS1 gene in fat tissue [1]. This mild reduction in insulin receptor substrate signaling can lead to subtle increases in blood pressure and circulating triglycerides [2]. It also correlates with a modest reduction in protective HDL cholesterol levels [2]. While the increase in coronary artery disease risk is small, adopting heart-healthy lifestyle habits remains highly beneficial.
Slightly higher risk of coronary artery disease; Mildly elevated triglycerides; Slightly lower HDL cholesterol.
Sample genotype: TT (Homozygous)
A less favorable metabolic and cardiovascular profile is associated with the T/T genotype. Having two risk alleles significantly reduces the expression of the IRS1 gene in adipose tissue, which can impair insulin sensitivity [1]. This genetic predisposition is robustly linked to higher circulating triglycerides and lower levels of protective HDL cholesterol [2]. Additionally, higher systolic and diastolic blood pressure are frequently observed [3]. Together, these metabolic factors contribute to an increased risk of developing coronary artery disease [1]. Emphasizing a diet low in saturated fats and engaging in regular aerobic exercise can help mitigate these genetic risks.
Increased risk of coronary artery disease; Elevated triglycerides and lower HDL cholesterol; Higher systolic and diastolic blood pressure.
Variants with shared genetic architecture
rs2943645 · IRS1 Gene · Chr 2 · Insulin Resistance Risk
rs2176040 · IRS1 Gene · Chr 2 · Metabolic Health
rs2943640 · IRS1 Gene · Chr 2 · Metabolic Health and Diabetes
Biological, clinical and population relevance of 95 loci for blood lipids.
Content updated August 2026.
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