Associations of polygenic risk scores for type 2 diabetes with metabolic measures in Pacific Islanders from Guam and Saipan.

Abstract

Several polygenic risk scores (PRSs) for type 2 diabetes (T2D) have been derived from genome-wide association studies (GWASs), but Pacific populations have generally not been represented in these GWASs. The aim of this study was to examine the association of PRS for T2D with diabetes and clinical measures in Pacific Islander populations from Guam and Saipan. We analyzed seven constructions of PRSs in 1990 participants in a GWAS from a community-based cross-sectional study of diabetes. Associations of T2D PRS with diabetes, maximum body mass index (BMI), fasting glucose, and HbA1c were examined with adjustment for age, sex, and the first four genetic principal components (PCs) from the GWAS (to account for population stratification). Insulin resistance/secretion measures were also analyzed in 989 participants without diabetes. All seven PRSs were strongly associated with T2D (p < 5 × 10^-9 for each); a 1-SD increase in the PRS was associated with 39-81% increase in the odds of T2D (i.e., standardized odds ratio [OR] ranging 1.39-1.81) adjusting for age, sex, and PCs. We also found that a 1-SD increase in the PRS was associated with 0.30-0.46 mmol/L higher fasting glucose, and with 2.68-4.63 mmol/mol higher HbA1c adjusting for age, sex, and PCs. We found no associations of PRSs with maximum BMI or insulin measures. All seven of the T2D polygenic risk scores evaluated associated significantly and strongly with diabetes, fasting glucose and HbA1c. These analyses suggest that T2D polygenic scores, as currently derived, have a certain degree of transferability to individuals from Pacific populations.