What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 5/10 evidence, 14 publications.
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Sample genotype (not yours): A/A
Lowest Risk of Type 2 Diabetes
Carrying two copies of the protective A allele is associated with the lowest risk of type 2 diabetes. This genotype provides the strongest genetic support for pancreatic beta-cell function.
What this genotype means: Significantly lower type 2 diabetes risk; Optimized insulin secretion.
Sample genotype (not yours): A/G
Reduced Risk of Type 2 Diabetes
Carrying one copy of the protective A allele is linked to a lower risk of developing type 2 diabetes. This genotype supports more efficient insulin secretion and better blood sugar control.
What this genotype means: Slightly lower type 2 diabetes risk; Enhanced insulin secretion.
Sample genotype (not yours): G/G
Typical Risk of Type 2 Diabetes
Carrying two copies of the common G allele is associated with typical baseline risk for type 2 diabetes. This genotype represents the standard genetic background for insulin secretion and blood sugar regulation.
What this genotype means: Typical insulin secretion; Standard type 2 diabetes risk.
Gene function and biological role
Gene Function: WFS1 encodes wolframin, an endoplasmic reticulum transmembrane glycoprotein. It plays a critical role in maintaining calcium homeostasis and managing cellular stress, particularly in pancreatic beta cells [1] [2]. Rare, severe mutations in WFS1 cause Wolfram syndrome, a rare genetic disorder characterized by childhood-onset diabetes mellitus, optic atrophy, and deafness [2]. However, common variations in this gene are associated with susceptibility to typical type 2 diabetes [1].
Variant Impact: An intronic change within the WFS1 gene defines rs10010131. While it does not alter the protein sequence directly, it is in strong linkage disequilibrium with functional variants that modulate WFS1 expression [3]. This genetic variation influences how well pancreatic beta cells manage endoplasmic reticulum stress and secrete insulin in response to glucose [4]. The minor A allele is widely recognized for its protective effect against metabolic dysfunction [5].
Key Insight: While rare mutations in this gene cause a severe, multi-system syndrome, common variants like this one simply nudge your everyday diabetes risk up or down.
Location: WFS1. Chromosome 4 · 4p16.1 · 6.3 Mb
Estimated prevalence by population
Global 13.5%; European 16.0%; African 12.0%; East Asian 0.4%; South Asian 8.4%; Americas 9.0%; Ashkenazi 10.4%; Finnish 18.4%; Middle Eastern 12.6%; Amish 37.6%.
Estimated AA genotype frequency.
Global 45.1%; European 48.0%; African 45.2%; East Asian 12.3%; South Asian 41.1%; Americas 42.0%; Ashkenazi 43.7%; Finnish 49.0%; Middle Eastern 45.8%; Amish 47.4%.
Estimated AG genotype frequency.
Global 41.3%; European 36.0%; African 42.8%; East Asian 87.2%; South Asian 50.5%; Americas 48.9%; Ashkenazi 46.0%; Finnish 32.6%; Middle Eastern 41.6%; Amish 15.0%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 4/10. Source: PMID 17603484. Lower Risk.
Insulin Secretion. Evidence: 4/10. Source: PMID 21127832. Higher Secretion.
Blood Glucose. Evidence: 5/10. Source: PMID 38116116. Lower Levels.
Endocrine & Reproductive
Pregnancy & Birth Complications
Gestational Diabetes. Evidence: 3/10. Source: PMID 18984664. Lower Risk.
Showing effects for A/G genotype
Showing effects for G/G genotype
Type 2 Diabetes. Evidence: 4/10. Source: PMID 17603484. Typical Risk.
Insulin Secretion. Evidence: 4/10. Source: PMID 21127832. Typical Secretion.
Blood Glucose. Evidence: 5/10. Source: PMID 38116116. Typical Levels.
Gestational Diabetes. Evidence: 3/10. Source: PMID 18984664. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Two copies of the protective A allele provide the maximum genetic defense at this locus. Multiple large-scale meta-analyses have confirmed that this genotype correlates with the lowest genetic risk of developing type 2 diabetes [1]. This double-dose of the protective allele is linked to significantly enhanced insulin secretion and superior pancreatic beta-cell function [2]. It also correlates with lower fasting blood glucose levels and a reduced risk of gestational diabetes [3] [4]. By optimizing how the endoplasmic reticulum handles cellular stress, this genotype helps maintain long-term metabolic resilience.
Significantly lower type 2 diabetes risk; Optimized insulin secretion.
Sample genotype: AG (Heterozygous)
One copy of the protective A allele combined with one G allele characterizes this genotype. Research indicates that this single copy is sufficient to confer a modest reduction in the risk of developing type 2 diabetes [1]. This protective effect is primarily driven by improved pancreatic beta-cell survival and more robust insulin secretion in response to glucose [2]. Additionally, a lower likelihood of experiencing gestational diabetes during pregnancy has been observed [3]. Because the A allele helps the endoplasmic reticulum in pancreatic cells manage cellular stress more effectively, it provides a natural buffer against metabolic strain.
Slightly lower type 2 diabetes risk; Enhanced insulin secretion.
Sample genotype: GG (Homozygous)
Two copies of the common G allele represent the standard genetic background at this locus. Large-scale genetic studies and meta-analyses have established that this genotype represents the standard baseline risk for developing type 2 diabetes [1]. Pancreatic beta-cell function and standard insulin secretion patterns remain typical under normal physiological conditions [2]. Unlike rare pathogenic mutations in the WFS1 gene, this common variant does not cause Wolfram syndrome or severe monogenic diabetes [3]. It simply represents the standard genetic baseline, meaning that maintaining a healthy diet and active lifestyle remains the primary way to support metabolic health.
Typical insulin secretion; Standard type 2 diabetes risk.
Variants with shared genetic architecture
rs1801212 · WFS1 Gene · Chr 4 · Type 2 Diabetes Risk
rs1801214 · WFS1 Gene · Chr 4 · Type 2 Diabetes Risk
rs734312 · WFS1 Gene · Chr 4 · Type 2 Diabetes Risk
Common variants in WFS1 confer risk of type 2 diabetes.
Monogenic models: what have the single gene disorders taught us?
Common type 2 diabetes risk gene variants associate with gestational diabetes.
Content updated August 2026.
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