A genome-wide study of the effect of alcohol consumption on the risk of type 2 diabetes
Bibliographic record
Abstract
The relationship between alcohol consumption and type 2 diabetes risk is often described as a J- or U-shaped curve, with moderate drinkers having a lower risk compared to non-drinkers and heavy drinkers. However, this protective effect appears to be more pronounced in women than in men, suggesting a potential interaction between sex-specific factors and alcohol metabolism. We conducted an interaction genome-wide association study (GWAS) to identify genetic variants that modify the relationship between alcohol consumption and type 2 diabetes risk in a sex-specific manner. We utilized data from the UK Biobank in a case-control approach including 309,568 individuals to investigate the three-way interaction between genetic variants, alcohol consumption, and sex on type 2 diabetes risk. We identified genetic variant rs78681203, located between the FOXO6 and EDN2 genes, with a significant sex-specific interaction with alcohol consumption (interaction p = 2.85 × 10 −8 ). The T allele of rs78681203 was associated with an increased risk of type 2 diabetes in women consuming 0 to <4 UK units/week (OR = 1.19, 95% CI: 1.07–1.34) but had a protective effect in women consuming 4 to <28 UK units/week (OR = 0.81, 95% CI: 0.69–0.95). Conversely, in men, the T allele was associated with a higher risk of type 2 diabetes in the 4 to <28 UK units/week group (OR = 1.19, 95% CI: 1.08–1.32) and had a protective effect in the 0 to <4 UK units/week group (OR = 0.85, 95% CI: 0.74–0.99). Our findings suggest that genetic variation may play a role in the differential effects of alcohol consumption on type 2 diabetes risk between men and women. Further replication and mechanistic studies are needed to confirm and clarify the role of the identified genetic variant. • Genetic variant rs78681203 interacts with alcohol consumption on sex-specific type 2 diabetes risk. • The T allele of rs78681203 protects women with higher alcohol intake from type 2 diabetes but increases risk in men. • rs78681203 is located between FOXO6 and EDN2, genes linked to glucose homeostasis and vascular function, respectively. • Genetic variation can help clarify alcohol’s differing effects on type 2 diabetes risk in men and women.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".