rs10738708 (TUSC1): Beta Cell Function & Diabetes
Key takeaways
- rs10738708 sits near RN7SKP120 and TUSC1, a region studied in American Indians for links to pancreatic beta cell function and diabetes
- American Indians in the Strong Heart Family Study face a diabetes prevalence of 34-68%, more than triple the 9.3% U.S. average
- A scan of ~200,000 cardiometabolic variants identified 26 loci tied to corrected beta cell function, including 8 previously unreported regions
- Evidence comes from one study in a specific population and has not been reported as replicated across other ancestry groups
Key takeaways
- rs10738708 sits near RN7SKP120 and TUSC1, a region studied in American Indians for links to pancreatic beta cell function and type 2 diabetes
- American Indians in the Strong Heart Family Study face a diabetes prevalence estimated at 34-68%, more than triple the 9.3% U.S. average
- A scan of approximately 200,000 cardiometabolic variants identified 26 loci significantly tied to corrected beta cell function (cHOMA-B), including 8 that were previously unreported
- Evidence comes from a single study in one ancestral population; replication in other groups has not been reported in the available literature
What the research says
The Strong Heart Family Study (SHFS), a family-based cohort of American Indians from Arizona, Oklahoma, and North and South Dakota, screened approximately 200,000 cardiometabolic genetic variants for associations with three traits: corrected HOMA-B (cHOMA-B - a measure of pancreatic beta cell function adjusted for insulin resistance), HOMA-IR (a standard measure of how resistant the body is to insulin), and incident type 2 diabetes mellitus. The study enrolled 1,923 participants without diabetes at baseline, 256 of whom developed diabetes during follow-up; a separate Southwestern Arizona cohort of 3,244 individuals served as a partial replication sample. Twenty-six loci reached genome-wide significance for cHOMA-B after strict Bonferroni correction (P < 4.13 × 10−7), eight of which were considered novel at publication, with the strongest single signal observed near PARP8 (rs2961831, P = 6.39 × 10−9).
Reported associations
- Pancreatic beta cell function (cHOMA-B): The RN7SKP120-TUSC1 region was included in a cardiometabolic variant screen that identified 26 genome-wide significant loci for corrected beta cell function in American Indians; specific effect sizes for rs10738708 are not reported in the available study excerpt
- Insulin resistance (HOMA-IR): Variants near candidate diabetes genes GCK and KCNQ1 showed nominal associations with HOMA-IR in the same cohort; HOMA-IR was evaluated as a secondary trait across all tested loci
- Incident type 2 diabetes: 256 new diabetes cases arose among 1,923 baseline-eligible participants during follow-up; variants significantly associated with cHOMA-B were also evaluated for diabetes incidence
Evidence quality
All available evidence derives from a single study (primary analysis: n = 1,923; partial replication sample: n = 3,244) conducted exclusively in American Indian participants. Multiple testing was controlled via Bonferroni correction (P < 4.13 × 10−7 across approximately 200,000 variants). The study authors explicitly note that most loci identified in European-ancestry populations have not replicated in American Indians, and vice versa, so generalizability to other ancestral groups is uncertain. No effect size specific to rs10738708 is reported in the available study excerpt. Evidence for this locus should be considered preliminary until independently replicated in diverse populations.
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is TUSC1 and why is it studied in diabetes research?
TUSC1 (Tumor Suppressor Candidate 1) is a gene near RN7SKP120 that has been included in cardiometabolic variant screens. Research in American Indian populations has investigated this chromosomal region for potential links to pancreatic beta cell function, which plays a central role in insulin production and the development of type 2 diabetes.
Is rs10738708 associated with type 2 diabetes?
The RN7SKP120-TUSC1 region was included in a large cardiometabolic variant study in American Indians that examined type 2 diabetes as one of its outcomes. Specific effect size data for rs10738708 were not detailed in the available study excerpt, so the strength of any association for this particular variant remains unclear from the current evidence.
What is HOMA-B and why do researchers use it in diabetes genetics?
HOMA-B (Homeostatic Model Assessment of Beta Cell Function) is a formula that estimates how effectively the pancreatic cells responsible for producing insulin are working. Because reduced beta cell function is an early step in type 2 diabetes, it is widely used as a measurable trait in genetic association studies.
Do these findings apply to people outside American Indian populations?
The research was conducted specifically in American Indians enrolled in the Strong Heart Family Study. The study's own authors note that genetic risk variants for diabetes often differ across ancestral groups, and results from this population may not generalize to others without independent replication.
What is the Strong Heart Family Study?
The Strong Heart Family Study (SHFS) is a family-based cohort of American Indians recruited from tribes across Arizona, Oklahoma, and North and South Dakota. It was designed to study cardiovascular and metabolic disease risk, including the genetic factors underlying type 2 diabetes in a population facing unusually high diabetes rates.