What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 8/10 evidence, 33 publications.
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Sample genotype (not yours): A/A
Typical Risk of Type 2 Diabetes
Presence of the common A allele is associated with standard blood sugar levels and typical metabolic health.
What this genotype means: Standard fasting blood glucose levels; No elevated risk of thiazide-induced diabetes; Slightly higher baseline body mass index.
Sample genotype (not yours): A/T
Moderately Increased Risk of Type 2 Diabetes
A single copy of the T allele is linked to a roughly 1.4-fold increase in the risk of developing type 2 diabetes.
What this genotype means: Roughly 1.4x higher risk of type 2 diabetes; Slightly elevated fasting blood glucose; Increased risk of diabetes when taking thiazide diuretics.
Sample genotype (not yours): T/T
Significantly Increased Risk of Type 2 Diabetes
Double copies of the T allele are associated with a nearly 1.9-fold increase in the risk of type 2 diabetes.
What this genotype means: Nearly 1.9x higher risk of type 2 diabetes; Elevated fasting blood glucose levels; Significantly increased risk of diabetes from thiazide diuretics.
Gene function and biological role
Gene Function: The TCF7L2 gene encodes a transcription factor that plays a critical role in the Wnt signaling pathway, which is vital for cell development and growth. In the pancreas, this protein is a key regulator of insulin secretion and glucose metabolism [1]. It influences the development of pancreatic beta cells, which are responsible for producing and releasing insulin in response to blood sugar changes [2]. Variations in this gene can alter its expression levels, directly affecting how well the pancreas can secrete insulin to maintain healthy glucose levels [3]. Consequently, TCF7L2 is widely recognized as one of the most influential genes affecting susceptibility to metabolic conditions [4].
Variant Impact: The rs4506565 variant is located within an intron, or non-coding region, of the TCF7L2 gene. Although it does not directly change the structure of the protein, this genetic change acts as a regulatory signal that alters gene expression [1]. This specific variation is highly correlated with another well-known metabolic variant, rs7903146, sharing a high degree of inheritance overlap [3]. The presence of the variant allele is strongly associated with elevated fasting blood glucose levels and impaired insulin secretion [2]. Research across diverse global populations has consistently highlighted this variant as a major genetic marker for metabolic health [4].
Key Insight: Although the T allele significantly increases the risk of type 2 diabetes, it is actually associated with a slightly lower average body mass index.
Location: TCF7L2. Chromosome 10 · 10q25.2 · 113.0 Mb
Estimated prevalence by population
Global 45.1%; European 46.9%; African 29.7%; East Asian 94.8%; South Asian 48.2%; Americas 49.3%; Ashkenazi 47.6%; Finnish 61.3%; Middle Eastern 33.8%; Amish 50.3%.
Estimated AA genotype frequency.
Global 42.8%; European 43.2%; African 49.6%; East Asian 5.2%; South Asian 42.5%; Americas 41.8%; Ashkenazi 42.8%; Finnish 34.0%; Middle Eastern 48.7%; Amish 41.2%.
Estimated AT genotype frequency.
Global 12.1%; European 9.9%; African 20.7%; East Asian 0.1%; South Asian 9.4%; Americas 8.9%; Ashkenazi 9.6%; Finnish 4.7%; Middle Eastern 17.5%; Amish 8.4%.
Estimated TT genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 17554300. Typical Risk.
Fasting Glucose. Evidence: 8/10. Source: PMID 20081858. Typical Levels.
Obesity & Body Composition
Body Mass Index. Evidence: 8/10. Source: PMID 30239722. Slightly Higher BMI.
Pharmacogenomics
Cardiovascular Drug Response
Thiazide Diabetes Risk. Evidence: 5/10. Source: PMID 24128935. Typical Risk.
Showing effects for A/T genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 17554300. ~1.4x Increased Risk.
Fasting Glucose. Evidence: 8/10. Source: PMID 20081858. Slightly Elevated.
Body Mass Index. Evidence: 8/10. Source: PMID 30239722. Typical BMI.
Thiazide Diabetes Risk. Evidence: 5/10. Source: PMID 24128935. Increased Risk.
Showing effects for T/T genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 17554300. ~1.9x Increased Risk.
Fasting Glucose. Evidence: 8/10. Source: PMID 20081858. Elevated Levels.
Body Mass Index. Evidence: 8/10. Source: PMID 30239722. Slightly Lower BMI.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Baseline genetic profiles for this specific marker in the TCF7L2 gene are characterized by typical metabolic function. Individuals with this combination typically maintain standard fasting blood glucose levels and normal insulin secretion [1]. While other genetic and lifestyle factors still play a major role in overall metabolic health, this specific variant does not add extra risk [2]. Interestingly, some studies suggest this genotype is associated with a slightly higher body mass index compared to carrying the T allele, though the effect size is very small [3]. When taking thiazide diuretics like hydrochlorothiazide for blood pressure, this group does not show an elevated risk of developing new-onset diabetes [4]. Maintaining a balanced diet and regular physical activity remains the most effective way to support metabolic wellness.
Standard fasting blood glucose levels; No elevated risk of thiazide-induced diabetes; Slightly higher baseline body mass index.
Sample genotype: AT (Heterozygous)
Moderate increases in susceptibility to metabolic challenges are common with this genetic profile. Having one copy of the T allele is linked to a 1.36 to 1.4-fold increase in the odds of developing type 2 diabetes [1]. This change is thought to influence how the TCF7L2 gene regulates insulin secretion in pancreatic beta cells, leading to slightly higher fasting blood sugar levels [2]. Additionally, clinical studies have noted that individuals with this genotype may have an increased risk of developing new-onset diabetes if treated with thiazide diuretics like hydrochlorothiazide [3]. On the other hand, some research indicates a minor association with a slightly lower body mass index compared to the common AA genotype [4]. Focusing on proactive lifestyle habits, such as a fiber-rich diet and routine exercise, can help manage blood sugar levels effectively.
Roughly 1.4x higher risk of type 2 diabetes; Slightly elevated fasting blood glucose; Increased risk of diabetes when taking thiazide diuretics.
Sample genotype: TT (Homozygous)
Elevated genetic risk for metabolic conditions is highly characteristic of this specific profile. Having two copies of the T allele is linked to an approximate 1.9-fold increase in the risk of developing type 2 diabetes [1]. The genetic variation alters TCF7L2 expression, which directly impacts the pancreas's ability to secrete insulin in response to glucose [2]. Consequently, individuals with this profile often exhibit higher fasting blood glucose levels [3]. Furthermore, there is a pronounced risk of developing new-onset diabetes when using thiazide diuretics such as hydrochlorothiazide for high blood pressure [4]. Despite these metabolic risks, some studies have observed a slight correlation with a lower body mass index [5]. Prioritizing metabolic health through regular cardiovascular exercise, monitoring blood sugar, and eating a balanced diet can significantly mitigate these genetic risks.
Nearly 1.9x higher risk of type 2 diabetes; Elevated fasting blood glucose levels; Significantly increased risk of diabetes from thiazide diuretics.
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
Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
Impact of TCF7L2 single nucleotide polymorphisms on hydrochlorothiazide-induced diabetes.
Content updated August 2026.
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