The Journal of clinical endocrinology and metabolism · 2019
Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАПоддержка правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод пока не подготовлен
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Hivert Marie-France, Christophi Costas A, Jablonski Kathleen A, Edelstein Sharon L, Kahn Steven E, Golden Sherita Hill, Dagogo-Jack Samuel, Mather Kieren J, Luchsinger José A, Caballero A Enrique, Barrett-Connor Elizabeth, Knowler William C, Florez Jose C, Herman William H
Аннотация
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.
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.