HbA1c levels are higher in African Americans (AA) than Non-Hispanic Whites (NHW). We investigated whether genetics could explain this difference in Diabetes Prevention Program (DPP) participants.
We tested 1) genetic variants causing hemoglobinopathies; 2) a genetic risk score (GRS) based on 60 variants associated with HbA1c from genome-wide association meta-analysis; and 3) Principal Components (PC) factors that capture continental ancestry derived from genetic markers distributed across the genome.
Of 2,658 eligible DPP participants, 537 (20%) self-identified as AA and 1,476 (56%) as NHW. Despite comparable fasting and 2h-glucose levels, AA had higher HbA1c (mean±SD= 6.2±0.6%) compared to NHW (5.8±0.4%; P<0.001). In AA, the genetic variant causing sickle cell trait was associated with higher HbA1c (β(SE)= +0.44(0.08)%; P=2.1x10-4). The GRS was associated with HbA1c in both AA and NHW. Self-identified AA were distributed along the first PC axis, as expected in mixed ancestry populations. The first PC explained 60% of the 0.4% difference in HbA1c between AA and NHW, while the sickle cell variant explained 16%, and GRS explained 14%.
A large proportion of HbA1c difference between AA and NHW was associated with the first PC factor, suggesting that unidentified genetic markers influence HbA1c in AA, in addition to non-genetic factors.