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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.
SUBMITTER: Hivert MF
PROVIDER: S-EPMC6300069 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Hivert Marie-France MF Christophi Costas A CA Jablonski Kathleen A KA Edelstein Sharon L SL Kahn Steven E SE Golden Sherita Hill SH Dagogo-Jack Samuel S Mather Kieren J KJ Luchsinger José A JA Caballero A Enrique AE Barrett-Connor Elizabeth E Knowler William C WC Florez Jose C JC Herman William H WH
The Journal of clinical endocrinology and metabolism 20190201 2
<h4>Purpose</h4>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.<h4>Methods</h4>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 dist ...[more]