Purpose: 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. Methods: 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. Results: 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 (beta(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%. Conclusions: 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.
Reference Type
Journal Article
Periodical Full
The Journal of clinical endocrinology and metabolism
Publication Year
2019
Publication Date
Oct 24
Volume
104
Issue
2
Start Page
328
Other Pages
336
Place of Publication
United States
ISSN/ISBN
1945-7197
Accession Number
PMID: 30358859
Document Object Index
10.1210/jc.2018-01416 [doi]
PMID
30358859
PMCID
PMC6300069