What you carry at this position in your DNA and what research says about it.
Metabolic Health and Body Fat: 8/10 evidence, 17 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): C/C
Higher Body Fat but Lower Diabetes Risk
A unique genetic trade-off characterizes this profile, linking a higher percentage of body fat to a highly favorable metabolic state. Lower risks of type 2 diabetes, reduced triglycerides, and improved insulin sensitivity are commonly observed.
What this genotype means: Favorable metabolic profile; Higher subcutaneous body fat; Lower risk of type 2 diabetes.
Sample genotype (not yours): C/T
Typical Metabolic Profile and Body Fat
An intermediate balance of body fat distribution and metabolic risk factors is typical for this genotype. Most metabolic markers, including insulin sensitivity and blood lipids, fall within the average range.
What this genotype means: Typical metabolic profile; Average body fat distribution; Standard risk of type 2 diabetes.
Sample genotype (not yours): T/T
Higher Diabetes Risk but Lower Body Fat
A lower percentage of body fat is paired with an unfavorable metabolic profile in this genotype. Higher risks of type 2 diabetes, elevated triglycerides, and reduced insulin sensitivity are common characteristics.
What this genotype means: Unfavorable metabolic profile; Lower subcutaneous body fat; Increased risk of type 2 diabetes.
Gene function and biological role
Gene Function: The IRS1 gene encodes insulin receptor substrate 1, a key signaling adapter protein that transmits signals from the insulin receptor to intracellular pathways [1]. This protein is essential for mediating the effects of insulin on glucose uptake in skeletal muscle and adipose tissue [1]. Proper functioning of this pathway is crucial for maintaining systemic glucose homeostasis and preventing insulin resistance [2]. Genetic variations that alter the expression or activity of this protein can disrupt metabolic balance and fat storage capacity [2]. Consequently, this gene is a major locus of interest in research on type 2 diabetes, obesity, and cardiovascular disease [3].
Variant Impact: The intergenic variant rs2943650 is located approximately 500 kilobases upstream of the IRS1 gene and acts as a regulatory element [1]. The T allele of this variant is associated with significantly reduced expression of IRS1 in subcutaneous adipose tissue [1]. This reduction in expression impairs the safe storage of fat under the skin, leading to ectopic fat deposition in visceral areas and skeletal muscle [1]. Conversely, the C allele supports robust IRS1 expression, allowing for healthy subcutaneous fat expansion [1]. As a result, this single nucleotide polymorphism serves as a genetic pivot between physical fat accumulation and metabolic health [2].
Key Insight: Having less body fat does not always mean better health; this variant shows that a lower body fat percentage can sometimes pair with higher diabetes risk due to how fat is stored.
Location: IRS1. Chromosome 2 · 2q36.3 · 226.2 Mb
Estimated prevalence by population
Global 18.2%; European 13.2%; African 35.5%; East Asian 0.6%; South Asian 6.9%; Americas 8.4%; Ashkenazi 8.4%; Finnish 13.9%; Middle Eastern 24.3%; Amish 18.7%.
Estimated CC genotype frequency.
Global 44.9%; European 46.2%; African 48.2%; East Asian 14.0%; South Asian 38.7%; Americas 41.2%; Ashkenazi 41.2%; Finnish 46.8%; Middle Eastern 50.0%; Amish 49.1%.
Estimated CT genotype frequency.
Global 36.9%; European 40.6%; African 16.3%; East Asian 85.5%; South Asian 54.4%; Americas 50.3%; Ashkenazi 50.4%; Finnish 39.3%; Middle Eastern 25.7%; Amish 32.3%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 32541925. Lower Risk.
Obesity & Body Composition
Body Fat Percentage. Evidence: 8/10. Source: PMID 37867527. Higher.
Lipids & Cholesterol
Triglycerides. Evidence: 8/10. Source: PMID 35213538. Lower Levels.
Gout & Uric Acid
Uric Acid Levels. Evidence: 7/10. Source: PMID 33356394. Lower Levels.
Showing effects for C/T genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 32541925. Typical Risk.
Body Fat Percentage. Evidence: 8/10. Source: PMID 37867527. Typical.
Triglycerides. Evidence: 8/10. Source: PMID 35213538. Typical Levels.
Uric Acid Levels. Evidence: 7/10. Source: PMID 33356394. Typical Levels.
Showing effects for T/T genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 32541925. Increased Risk.
Body Fat Percentage. Evidence: 8/10. Source: PMID 37867527. Lower.
Triglycerides. Evidence: 8/10. Source: PMID 35213538. Higher Levels.
Uric Acid Levels. Evidence: 7/10. Source: PMID 33356394. Higher Levels.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Adipose tissue distribution plays a critical role in determining overall metabolic health. Research near the IRS1 gene locus shows that carrying two copies of the C allele leads to increased subcutaneous fat storage, particularly under the skin rather than around internal organs [1]. This specific fat distribution pattern is benign and acts as a safe metabolic sink, preventing lipids from accumulating in liver or muscle tissues [1]. Consequently, despite having a higher overall body fat percentage, individuals with this genotype exhibit excellent insulin sensitivity and a lower risk of type 2 diabetes [2]. Blood lipid profiles also tend to be highly favorable, characterized by lower circulating triglycerides and higher HDL cholesterol levels [3]. Furthermore, lower levels of uric acid are typically maintained, reducing the risk of gout and related cardiovascular strain [4]. This phenomenon is often referred to as metabolically healthy obesity or favorable adiposity.
Favorable metabolic profile; Higher subcutaneous body fat; Lower risk of type 2 diabetes.
Sample genotype: CT (Heterozygous)
Carrying one copy of each allele results in an intermediate metabolic and physical profile. Fat distribution and storage capacity in subcutaneous depots generally align with population averages. Insulin sensitivity and the risk of developing type 2 diabetes are not significantly elevated or reduced by this genetic factor [1]. Blood lipid measurements, including triglycerides and HDL cholesterol, typically remain within normal baseline ranges [2]. Similarly, circulating uric acid levels do not show a strong genetic bias toward being high or low [3]. This balanced genetic background means that lifestyle choices, such as diet and physical activity, play the dominant role in shaping metabolic outcomes. Maintaining a balanced diet and regular exercise is highly effective for supporting long-term cardiovascular and metabolic wellness.
Typical metabolic profile; Average body fat distribution; Standard risk of type 2 diabetes.
Sample genotype: TT (Homozygous)
Limiting the storage capacity of subcutaneous fat tissue is a primary feature of this genetic profile [1]. When subcutaneous fat cannot expand safely, excess lipids are diverted to visceral depots around internal organs and into skeletal muscle [1]. This ectopic fat deposition leads to impaired insulin signaling and a significantly higher risk of developing type 2 diabetes [2]. Blood lipid profiles are also adversely affected, showing elevated triglycerides and lower levels of protective HDL cholesterol [3]. Additionally, higher circulating levels of uric acid are common, which can increase the risk of gout and cardiovascular strain [4]. Despite having a lower overall body fat percentage, the underlying metabolic environment is less favorable. Prioritizing cardiovascular health through regular physical activity and a low-glycemic diet is particularly beneficial for managing these risks.
Unfavorable metabolic profile; Lower subcutaneous body fat; Increased risk of type 2 diabetes.
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
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com