Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program

Marie France Hivert, Costas A. Christophi, Kathleen A. Jablonski, Sharon L. Edelstein, Steven E. Kahn, Sherita Hill Golden, Samuel Dagogo-Jack, Kieren Mather, José A. Luchsinger, A. Enrique Caballero, Elizabeth Barrett-Connor, William C. Knowler, Jose C. Florez, William H. Herman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)328-336
Number of pages9
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number2
DOIs
StatePublished - Feb 1 2019

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Medical problems
Genetic Markers
African Americans
Genes
Glucose
Sickle Cell Trait
Hemoglobinopathies
Genome-Wide Association Study
Meta-Analysis
Fasting
Genome
Population

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Hivert, M. F., Christophi, C. A., Jablonski, K. A., Edelstein, S. L., Kahn, S. E., Golden, S. H., ... Herman, W. H. (2019). Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program. The Journal of clinical endocrinology and metabolism, 104(2), 328-336. https://doi.org/10.1210/jc.2018-01416

Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program. / Hivert, Marie France; Christophi, Costas A.; Jablonski, Kathleen A.; Edelstein, Sharon L.; Kahn, Steven E.; Golden, Sherita Hill; Dagogo-Jack, Samuel; Mather, Kieren; Luchsinger, José A.; Caballero, A. Enrique; Barrett-Connor, Elizabeth; Knowler, William C.; Florez, Jose C.; Herman, William H.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 2, 01.02.2019, p. 328-336.

Research output: Contribution to journalArticle

Hivert, MF, Christophi, CA, Jablonski, KA, Edelstein, SL, Kahn, SE, Golden, SH, Dagogo-Jack, S, Mather, K, Luchsinger, JA, Caballero, AE, Barrett-Connor, E, Knowler, WC, Florez, JC & Herman, WH 2019, 'Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program', The Journal of clinical endocrinology and metabolism, vol. 104, no. 2, pp. 328-336. https://doi.org/10.1210/jc.2018-01416
Hivert, Marie France ; Christophi, Costas A. ; Jablonski, Kathleen A. ; Edelstein, Sharon L. ; Kahn, Steven E. ; Golden, Sherita Hill ; Dagogo-Jack, Samuel ; Mather, Kieren ; Luchsinger, José A. ; Caballero, A. Enrique ; Barrett-Connor, Elizabeth ; Knowler, William C. ; Florez, Jose C. ; Herman, William H. / Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program. In: The Journal of clinical endocrinology and metabolism. 2019 ; Vol. 104, No. 2. pp. 328-336.
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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.",
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AU - Hivert, Marie France

AU - Christophi, Costas A.

AU - Jablonski, Kathleen A.

AU - Edelstein, Sharon L.

AU - Kahn, Steven E.

AU - Golden, Sherita Hill

AU - Dagogo-Jack, Samuel

AU - Mather, Kieren

AU - Luchsinger, José A.

AU - Caballero, A. Enrique

AU - Barrett-Connor, Elizabeth

AU - Knowler, William C.

AU - Florez, Jose C.

AU - Herman, William H.

PY - 2019/2/1

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N2 - 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.

AB - 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.

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