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A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A 1c With Implications for Glycemic Status in U.S. Hispanics/Latinos.
- Source :
-
Diabetes care [Diabetes Care] 2019 Sep; Vol. 42 (9), pp. 1784-1791. Date of Electronic Publication: 2019 Jun 18. - Publication Year :
- 2019
-
Abstract
- Objective: We aimed to identify hemoglobin A <subscript>1c</subscript> (HbA <subscript>1c</subscript> )-associated genetic variants and examine their implications for glycemic status evaluated by HbA <subscript>1c</subscript> in U.S. Hispanics/Latinos with diverse genetic ancestries.<br />Research Design and Methods: We conducted a genome-wide association study (GWAS) of HbA <subscript>1c</subscript> 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.<br />Results: Our GWAS and replication analyses showed 10 previously known and novel loci associated with HbA <subscript>1c</subscript> at genome-wide significance levels ( P < 5.0 × 10 <superscript>-8</superscript> ). 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 <subscript>1c</subscript> levels (β = -0.31% [-3.4 mmol/mol]) and -0.35% [-3.8 mmol/mol] per minor allele, respectively) compared with other HbA <subscript>1c</subscript> -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 <subscript>1c</subscript> 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 <subscript>1c</subscript> -lowering alleles and noncarriers, whereas the prevalence of hyperglycemia defined using HbA <subscript>1c</subscript> was significantly lower in carriers than in noncarriers (12.2% vs. 28.4%, P < 0.001). After recalibration of the HbA <subscript>1c</subscript> 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).<br />Conclusions: This study in U.S. Hispanics/Latinos found several ancestry-specific alleles associated with HbA <subscript>1c</subscript> through erythrocyte-related rather than glycemic-related pathways. The potential influences of these nonglycemic-related variants need to be considered when the HbA <subscript>1c</subscript> test is performed.<br /> (© 2019 by the American Diabetes Association.)
- Subjects :
- Adult
Alleles
Blood Glucose metabolism
Diabetes Mellitus ethnology
Fasting blood
Female
Genome-Wide Association Study
Glucose Tolerance Test
Hematologic Diseases ethnology
Humans
Hyperglycemia epidemiology
Hyperglycemia ethnology
Hyperglycemia genetics
Male
Middle Aged
Phenotype
Prediabetic State ethnology
Prediabetic State genetics
Prevalence
United States epidemiology
Diabetes Mellitus genetics
Genetic Variation genetics
Glycated Hemoglobin genetics
Hematologic Diseases genetics
Hispanic or Latino genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1935-5548
- Volume :
- 42
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Diabetes care
- Publication Type :
- Academic Journal
- Accession number :
- 31213470
- Full Text :
- https://doi.org/10.2337/dc19-0168