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Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program.
Citation | “Genetic Ancestry Markers And Difference In A1C Between African American And White In The Diabetes Prevention Program.”. The Journal Of Clinical Endocrinology And Metabolism, pp. 328-336. . |
Center | University of Michigan University of Washington |
Multicenter |
Multicenter
|
Author | Marie-France Hivert, Costas A Christophi, Kathleen A Jablonski, Sharon L Edelstein, Steven E Kahn, Sherita Hill Golden, Samuel Dagogo-Jack, Kieren J Mather, José A Luchsinger, Enrique Caballero, Elizabeth Barrett-Connor, William C Knowler, Jose C Florez, William H Herman |
Abstract |
Purpose: HbA1c levels are higher in blacks than non-Hispanic whites (NHWs). We investigated whether genetics could explain this difference in Diabetes Prevention Program (DPP) participants. Methods: We tested (i) genetic variants causing hemoglobinopathies, (ii) a genetic risk score (GRS) based on 60 variants associated with HbA1c from genome-wide association meta-analysis, and (iii) principal component (PC) factors that capture continental ancestry derived from genetic markers distributed across the genome. Results: Of 2658 eligible DPP participants, 537 (20%) self-identified as black and 1476 (56%) as NHW. Despite comparable fasting and 2-hour glucose levels, blacks had higher HbA1c (mean ± SD = 6.2 ± 0.6%) compared with NHWs (5.8 ± 0.4%; P < 0.001). In blacks, the genetic variant causing sickle cell trait was associated with higher HbA1c [β (SE) = +0.44 (0.08)%; P = 2.1 × 10-4]. The GRS was associated with HbA1c in both blacks and NHWs. Self-identified blacks 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 blacks and NHWs, whereas the sickle cell variant explained 16% and GRS explained 14%. Conclusions: A large proportion of HbA1c difference between blacks and NHWs was associated with the first PC factor, suggesting that unidentified genetic markers influence HbA1c in blacks in addition to nongenetic factors. |
Year of Publication |
2019
|
Journal |
The Journal of clinical endocrinology and metabolism
|
Volume |
104
|
Issue |
2
|
Number of Pages |
328-336
|
Date Published |
12/2019
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ISSN Number |
1945-7197
|
DOI |
10.1210/jc.2018-01416
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Alternate Journal |
J. Clin. Endocrinol. Metab.
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PMID |
30358859
|
PMCID |
PMC6300069
|
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