rs117267808 (GP2): Type 2 Diabetes Risk, East Asian
Key takeaways
- rs117267808 is a missense variant in GP2, a gene active in the pancreatic acinar cells that produce digestive enzymes.
- The risk allele is common in Japanese populations (above 5% frequency) but rare in Europeans (below 1%), meaning it was only discoverable through East Asian genetics research.
- It was identified as one of 28 novel type 2 diabetes loci in a Japanese-ancestry meta-analysis of over 190,000 individuals.
- Pancreatic acinar cell biology is a less commonly studied T2D pathway than the insulin-producing beta cells implicated by most other diabetes variants.
- No lifestyle or pharmacogenomic findings specific to this variant have been reported in the studies reviewed here.
Key takeaways
- rs117267808 is a missense variant in GP2, a gene expressed in pancreatic acinar cells (the cells that produce digestive enzymes), and is associated with type 2 diabetes risk.
- The risk allele is common in Japanese populations (minor allele frequency above 5%) but rare in Europeans (below 1%), making this signal undetectable in European-only studies.
- Discovery came from a Japanese-ancestry meta-analysis of 36,614 type 2 diabetes cases and 155,150 controls, where it was one of 28 newly identified risk loci.
- Pancreatic acinar cell biology is a less commonly studied pathway in type 2 diabetes genetics compared to the insulin-secreting beta cells most other T2D variants implicate.
- No lifestyle or pharmacogenomic findings specific to this variant appear in the studies reviewed here.
What the research says A meta-analysis of four genome-wide association studies (GWAS) in 36,614 type 2 diabetes (T2D) cases and 155,150 controls of Japanese ancestry identified rs117267808 as a missense variant (a DNA change that alters the protein sequence) in GP2, a gene related to pancreatic acinar cell function, at a novel locus meeting genome-wide significance PMID 30643254. Among 28 missense variants in high linkage disequilibrium (genetic correlation, r^2 > 0.6) with T2D lead signals in that study, this was one of three with especially stark frequency differences: common in Japanese individuals (minor allele frequency above 5%) but rare in Europeans (below 1%), illustrating how East Asian-focused studies can uncover risk variants that European cohorts would miss PMID 30643254. A specific effect size (odds ratio or beta coefficient) for rs117267808 is not reported in the provided study text.
Reported associations
- Type 2 diabetes: Identified as a novel susceptibility locus in a Japanese-ancestry meta-analysis (36,614 cases, 155,150 controls); the candidate causal mechanism is a missense change in GP2, a gene active in pancreatic acinar cells; the association met genome-wide significance PMID 30643254
Evidence quality The primary evidence for rs117267808 comes from a single Japanese-ancestry GWAS meta-analysis (36,614 T2D cases, 155,150 controls) that identified 88 T2D-associated loci and 115 independent signals, of which 28 loci, including the GP2 locus, were novel PMID 30643254. The variant met genome-wide significance thresholds, but no specific odds ratio or beta coefficient is provided in the study text, and explicit independent replication for this variant specifically is not described. Because the risk allele is very rare in Europeans (MAF below 1%), statistical power to replicate this signal in European cohorts is minimal even at large sample sizes. Subsequent large-scale meta-analyses have expanded the T2D genetic landscape: an East Asian meta-analysis in 77,418 cases and 356,122 controls reported 51 novel loci but does not specifically address this variant PMID 32541925; a multi-ethnic meta-analysis in 228,499 cases and 1,178,783 controls reported 286 previously unreported associations and also does not specifically describe this variant in the provided text PMID 33139954. A separate Japanese GWAS of 42 diseases in 212,453 individuals identified 25 novel loci across diseases and provides broader context for the East Asian genetic disease landscape, but does not specifically address rs117267808 PMID 33060566. Overall, evidence for this specific variant remains preliminary, resting on a single discovery analysis without confirmed independent replication in the studies provided here.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does the GP2 gene do?
GP2 encodes a protein expressed in pancreatic acinar cells, which are responsible for producing digestive enzymes. Its precise role in type 2 diabetes susceptibility is not yet fully understood, but the genetic signal at this locus suggests that acinar cell biology may contribute to disease risk.
Is rs117267808 linked to type 2 diabetes?
Yes. rs117267808 was identified as a genome-wide significant type 2 diabetes susceptibility variant in a meta-analysis of 36,614 Japanese-ancestry cases and 155,150 controls. It is a missense variant, meaning it changes the protein sequence of GP2.
Why is this variant more common in Japanese than in European populations?
Genetic variant frequencies differ naturally across ancestries due to population history. The risk allele at rs117267808 has a minor allele frequency above 5% in Japanese individuals but below 1% in Europeans, making it effectively undetectable in most European-focused studies.
Has this variant been confirmed in other populations?
The available studies do not report independent replication of rs117267808 in non-Japanese populations. Because the risk allele is very rare in Europeans, confirming this association in European cohorts would require extremely large sample sizes.
What makes pancreatic acinar cells relevant to type 2 diabetes?
Most type 2 diabetes genetics research has focused on the insulin-producing beta cells of the pancreas. Variants in acinar cell genes like GP2 point to a potentially distinct pathway involving the digestive enzyme-producing part of the pancreas, though the mechanism for rs117267808 has not been described in the reviewed studies.