1653-P: Association between Genetic Admixture Estimates for Five Ancestral Populations and Diabetes-Related Traits in Pacific Islanders

Abstract

Ecological studies have shown different risks for diabetes (DM) among many ethnic groups, but whether they are due to genetic or non-genetic factors is hard to dissect. We conducted a community-based study aimed at identifying risk factors for DM and related traits in Pacific Islanders from Guam and Saipan. We analyzed the genetic structure of our sample and estimated individual-level admixture using genome-wide SNP data (49,300 variants). We found that genetic ancestry largely derived from 5 populations, representing Marianas Islanders (MI) (mean % heritage, or μ=43%), East Asians (EA, μ=22%), Micronesians (MC, μ=19%), Europeans (EU, μ=13%), and Melanesians (ML, μ=3%). We then tested the association of ancestry estimates with DM, fasting glucose and fasting insulin levels in study participants (n=1,853). Covariates included age, sex and end-stage kidney disease. For fasting insulin, only nondiabetic subjects were used in analyses. All 3 traits were associated with genetic ancestry (p<e-4). EA was associated with lowest DM risk and lowest mean levels of glucose and insulin, while DM risk and fasting glucose were highest in MI. DM risk (measured as odds ratio [OR]) for MI vs. EA was 6.9 (95% CI=3.3-14.7). Mean difference (β) in fasting glucose and insulin for MI vs. EA was 0.83 and 0.76 s.d. units, respectively. MI had higher DM risk compared to MC (OR=1.79, p=0.022), but similar risk to EU and ML. MI had higher mean glucose vs. MC (β=0.23 s.d. units, p=0.014). However, MI had comparable insulin levels to EU and MC, but lower than ML (β=-1.37 s.d. units, p=0.0046). In summary, there were large and statistically significant differences in DM-related traits among Pacific Islanders with different genetic ancestral backgrounds. Although genetic ancestry estimates may still be confounded by shared environmental factors, the present findings suggest that admixture mapping may be a potentially powerful approach for identifying unique DM loci in Pacific Islanders. Disclosure W. Hsueh: None. P. Kumar: None. S. Safabakhsh: None. L. Jones: None. J. Curran: None. W.C. Knowler: None. R.G. Nelson: None. R.L. Hanson: None.