What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 5/10 evidence, 55 publications.
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Sample genotype (not yours): G/G
Typical Type 2 Diabetes Risk
Two copies of the common G allele are associated with typical blood sugar regulation and a standard risk of developing type 2 diabetes. This genetic profile is also linked to a normal response to common diabetes medications.
What this genotype means: Typical risk of type 2 diabetes; Standard response to sulfonylurea medications; No elevated risk of breast or prostate cancer.
Sample genotype (not yours): G/T
Moderately Increased Type 2 Diabetes Risk
One copy of the T allele is linked to a moderately increased risk of developing type 2 diabetes. It may also slightly affect how the body responds to certain blood sugar-lowering medications.
What this genotype means: ~1.3x increased risk of type 2 diabetes; Slightly reduced insulin secretion; Slightly lower response to sulfonylureas.
Sample genotype (not yours): T/T
Higher Type 2 Diabetes Risk
Two copies of the T allele are associated with a 1.5-fold to 2-fold increase in type 2 diabetes risk. This genetic profile is also linked to a significantly reduced response to sulfonylurea medications.
What this genotype means: ~1.5x to 2x increased risk of type 2 diabetes; Significantly reduced response to sulfonylureas; Slightly increased risk of aggressive prostate cancer in males.
Gene function and biological role
Gene Function: The TCF7L2 gene encodes transcription factor 7-like 2, a protein that plays a critical role in the Wnt signaling pathway [1]. This pathway is essential for regulating cell growth, development, and the maintenance of pancreatic beta cells, which produce insulin [2]. TCF7L2 is highly expressed in mature pancreatic islets, where it helps coordinate insulin secretion in response to glucose [3]. Variations in this gene can disrupt these pathways, leading to impaired insulin production and glucose intolerance [4]. Consequently, TCF7L2 is widely recognized as the most significant common genetic locus influencing type 2 diabetes susceptibility across diverse global populations [5].
Variant Impact: Located within an intron of the TCF7L2 gene, this single nucleotide polymorphism acts as a regulatory modifier [1]. Although it does not directly alter the amino acid sequence of the protein, this change is located in a regulatory region that influences gene expression [2]. The presence of the T allele is strongly associated with decreased insulin secretion and impaired beta-cell function [3]. This specific genetic change has been extensively replicated in dozens of clinical trials as a major risk factor for metabolic dysfunction [5]. It also alters how the body responds to sulfonylurea medications, which rely on functioning beta cells to stimulate insulin release [6].
Key Insight: This variant is the single strongest common genetic risk factor for type 2 diabetes, yet its impact can be significantly managed or even offset by proactive lifestyle choices like diet and exercise.
Location: TCF7L2. Chromosome 10 · 10q25.2 · 113.0 Mb
Estimated prevalence by population
Global 54.1%; European 51.5%; African 49.2%; East Asian 98.1%; South Asian 55.9%; Americas 55.0%; Ashkenazi 47.0%; Finnish 70.7%; Middle Eastern 44.4%; Amish 44.0%.
Estimated GG genotype frequency.
Global 38.4%; European 40.6%; African 41.9%; East Asian 1.9%; South Asian 37.7%; Americas 38.3%; Ashkenazi 43.1%; Finnish 26.8%; Middle Eastern 44.4%; Amish 44.7%.
Estimated GT genotype frequency.
Global 7.5%; European 8.0%; African 8.9%; East Asian < 0.1%; South Asian 6.4%; Americas 6.7%; Ashkenazi 9.9%; Finnish 2.5%; Middle Eastern 11.1%; Amish 11.3%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 5/10. Source: PMID 16415884. Typical Risk.
Pharmacogenomics
Diabetes Medication Response
Sulfonylurea Response. Evidence: 5/10. Source: PMID 17519421. Typical Response.
Cancer & Oncology
Breast Cancer
Breast Cancer. Evidence: 3/10. Source: PMID 23085767. Typical Risk.
Prostate Cancer
Prostate Cancer. Evidence: 3/10. Source: PMID 23085767. Typical Risk.
Showing effects for G/T genotype
Type 2 Diabetes. Evidence: 5/10. Source: PMID 16415884. ~1.3x Increased Risk.
Sulfonylurea Response. Evidence: 5/10. Source: PMID 17519421. Slightly Reduced.
Showing effects for T/T genotype
Type 2 Diabetes. Evidence: 5/10. Source: PMID 16415884. ~1.5x to 2x Risk.
Sulfonylurea Response. Evidence: 5/10. Source: PMID 17519421. Poorer Response.
Breast Cancer. Evidence: 3/10. Source: PMID 23085767. Slightly Increased.
Prostate Cancer. Evidence: 3/10. Source: PMID 23085767. Slightly Increased.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Islet function and insulin secretion are typically optimal with the G/G genotype, which represents the ancestral baseline. Large-scale genetic studies have consistently shown that this genotype is associated with a typical baseline risk of type 2 diabetes [1]. The TCF7L2 gene plays a crucial role in the Wnt signaling pathway, which is vital for the development and function of insulin-secreting beta cells in the pancreas [2]. Because this version of the gene functions normally, the pancreas is expected to produce insulin efficiently in response to glucose [3]. Additionally, individuals with this genotype tend to respond better to sulfonylurea medications if they ever require treatment for blood sugar control [4]. There is also no elevated risk of breast or aggressive prostate cancer associated with this genetic profile [5].
Typical risk of type 2 diabetes; Standard response to sulfonylurea medications; No elevated risk of breast or prostate cancer.
Sample genotype: GT (Heterozygous)
A single copy of the T risk allele is widely recognized as one of the strongest genetic predictors for type 2 diabetes [1]. This single-letter change in the TCF7L2 gene is thought to reduce the expression of key factors that help pancreatic beta cells secrete insulin efficiently [2]. As a result, the body may produce less insulin in response to meals, leading to a moderate rise in diabetes susceptibility [3]. Clinical studies indicate that carriers of this variant may also experience a slightly reduced response to sulfonylurea drugs, a common class of diabetes medication [4]. While this genotype slightly increases genetic predisposition, lifestyle factors like diet and exercise remain highly influential in determining actual health outcomes [5].
~1.3x increased risk of type 2 diabetes; Slightly reduced insulin secretion; Slightly lower response to sulfonylureas.
Sample genotype: TT (Homozygous)
Two copies of the T risk allele represent the strongest common genetic risk factor known for type 2 diabetes [1]. This genetic variation alters the regulation of the TCF7L2 gene, leading to impaired insulin secretion from the pancreatic beta cells [2]. Consequently, individuals with this genotype have a significantly higher likelihood of developing type 2 diabetes compared to those with the G/G genotype [3]. If diagnosed with diabetes, people with this genotype are also nearly twice as likely to experience treatment failure when taking sulfonylurea medications [4]. Some research also suggests a potential, slight increase in susceptibility to breast cancer and more aggressive forms of prostate cancer [5]. Maintaining a healthy weight and active lifestyle is particularly beneficial for individuals with this genetic profile to help mitigate these risks [6].
~1.5x to 2x increased risk of type 2 diabetes; Significantly reduced response to sulfonylureas; Slightly increased risk of aggressive prostate cancer in males.
Variants with shared genetic architecture
rs34872471 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
rs7901695 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
rs7903146 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.
Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes.
Association of TCF7L2 polymorphisms with type 2 diabetes in Mexico City.
Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study.
Content updated August 2026.
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