A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A
In: Diabetes care, Jg. 42 (2019-01-24), Heft 9
Online
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Zugriff:
OBJECTIVE: We aimed to identify hemoglobin A(1c) (HbA(1c))-associated genetic variants and examine their implications for glycemic status evaluated by HbA(1c) in U.S. Hispanics/Latinos with diverse genetic ancestries. RESEARCH DESIGN AND METHODS: We conducted a genome-wide association study (GWAS) of HbA(1c) in 9,636 U.S. Hispanics/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos, followed by a replication among 4,729 U.S. Hispanics/Latinos from three independent studies. RESULTS: Our GWAS and replication analyses showed 10 previously known and novel loci associated with HbA(1c) at genome-wide significance levels (P < 5.0 × 10(−8)). In particular, two African ancestry–specific variants, HBB-rs334 and G6PD-rs1050828, which are causal mutations for sickle cell disease and G6PD deficiency, respectively, had ∼10 times larger effect sizes on HbA(1c) levels (β = −0.31% [−3.4 mmol/mol]) and −0.35% [−3.8 mmol/mol] per minor allele, respectively) compared with other HbA(1c)-associated variants (0.03–0.04% [0.3–0.4 mmol/mol] per allele). A novel Amerindian ancestry–specific variant, HBM-rs145546625, was associated with HbA(1c) and hematologic traits but not with fasting glucose. The prevalence of hyperglycemia (prediabetes and diabetes) defined using fasting glucose or oral glucose tolerance test 2-h glucose was similar between carriers of HBB-rs334 or G6PD-rs1050828 HbA(1c)-lowering alleles and noncarriers, whereas the prevalence of hyperglycemia defined using HbA(1c) was significantly lower in carriers than in noncarriers (12.2% vs. 28.4%, P < 0.001). After recalibration of the HbA(1c) level taking HBB-rs334 and G6PD-rs1050828 into account, the prevalence of hyperglycemia in carriers was similar to noncarriers (31.3% vs. 28.4%, P = 0.28). CONCLUSIONS: This study in U.S. Hispanics/Latinos found several ancestry-specific alleles associated with HbA(1c) through erythrocyte-related rather than glycemic-related pathways. The potential influences of these nonglycemic-related variants need to be considered when the HbA(1c) test is performed.
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A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A
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Autor/in / Beteiligte Person: | Jee-Young, Moon ; Tin L, Louie ; Deepti, Jain ; Tamar, Sofer ; Claudia, Schurmann ; Jennifer E, Below ; Chao-Qiang, Lai ; M Larissa, Aviles-Santa ; Gregory A, Talavera ; Caren E, Smith ; Lauren E, Petty ; Erwin P, Bottinger ; Yii-Der Ida, Chen ; Kent D, Taylor ; Martha L, Daviglus ; Jianwen, Cai ; Tao, Wang ; Katherine L, Tucker ; José M, Ordovás ; Craig L, Hanis ; Ruth J F, Loos ; Neil, Schneiderman ; Jerome I, Rotter ; Robert C, Kaplan ; Qibin, Qi |
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Zeitschrift: | Diabetes care, Jg. 42 (2019-01-24), Heft 9 |
Veröffentlichung: | 2019 |
Medientyp: | unknown |
ISSN: | 1935-5548 (print) |
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