Dataset Information

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A_1c With Implications for Glycemic Status in U.S. Hispanics/Latinos.

ABSTRACT: 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 (? = -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.

SUBMITTER: Moon JY

PROVIDER: S-EPMC6702612 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A<sub>1c</sub> With Implications for Glycemic Status in U.S. Hispanics/Latinos.

Moon Jee-Young JY Louie Tin L TL Jain Deepti D Sofer Tamar T Schurmann Claudia C Below Jennifer E JE Lai Chao-Qiang CQ Aviles-Santa M Larissa ML Talavera Gregory A GA Smith Caren E CE Petty Lauren E LE Bottinger Erwin P EP Chen Yii-Der Ida YI Taylor Kent D KD Daviglus Martha L ML Cai Jianwen J Wang Tao T Tucker Katherine L KL Ordovás José M JM Hanis Craig L CL Loos Ruth J F RJF Schneiderman Neil N Rotter Jerome I JI Kaplan Robert C RC Qi Qibin Q

Diabetes care 20190618 9

<h4>Objective</h4>We aimed to identify hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>)-associated genetic variants and examine their implications for glycemic status evaluated by HbA<sub>1c</sub> in U.S. Hispanics/Latinos with diverse genetic ancestries.<h4>Research design and methods</h4>We conducted a genome-wide association study (GWAS) of HbA<sub>1c</sub> in 9,636 U.S. Hispanics/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos, followed by a replication among 4 ...[more]

PMID: 31213470

Similar Datasets

Project description:ObjectiveThe aim of this study was to compare the ability of American Diabetes Association (ADA) diagnostic criteria to identify U.S. Hispanics/Latinos from diverse heritage groups with probable diabetes mellitus and assess cardiovascular risk factor correlates of those criteria.MethodsCross-sectional analysis of data from 15,507 adults from 6 Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos. The prevalence of probable diabetes mellitus was estimated using individual or combinations of ADA-defined cut points. The sensitivity and specificity of these criteria at identifying diabetes mellitus from ADA-defined prediabetes and normoglycemia were evaluated. Prevalence ratios of hypertension, abnormal lipids, and elevated urinary albumin-creatinine ratio for unrecognized diabetes mellitus-versus prediabetes and normoglycemia-were calculated.ResultsAmong Hispanics/Latinos (mean age, 43 years) with diabetes mellitus, 39.4% met laboratory test criteria for probable diabetes, and the prevalence varied by heritage group. Using the oral glucose tolerance test as the gold standard, the sensitivity of fasting plasma glucose (FPG) and hemoglobin A1c-alone or in combination-was low (18, 23, and 33%, respectively) at identifying probable diabetes mellitus. Individuals who met any criterion for probable diabetes mellitus had significantly higher (P<.05) prevalence of most cardiovascular risk factors than those with normoglycemia or prediabetes, and this association was not modified by Hispanic/Latino heritage group.ConclusionFPG and hemoglobin A1c are not sensitive (but are highly specific) at detecting probable diabetes mellitus among Hispanics/Latinos, independent of heritage group. Assessing cardiovascular risk factors at diagnosis might prompt multitarget interventions and reduce health complications in this young population.Abbreviations2hPG = 2-hour post-glucose load plasma glucose ADA = American Diabetes Association BMI = body mass index CV = cardiovascular FPG = fasting plasma glucose HbA1c = hemoglobin A1c HCHS/SOL = Hispanic Community Health Study/Study of Latinos HDL-C = high-density-lipoprotein cholesterol NGT = normal glucose tolerance NHANES = National Health and Nutrition Examination Survey OGTT = oral glucose tolerance test TG = triglyceride UACR = urine albumin-creatinine ratio.

Dataset Information

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A_1c With Implications for Glycemic Status in U.S. Hispanics/Latinos.

Publications

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A<sub>1c</sub> With Implications for Glycemic Status in U.S. Hispanics/Latinos.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A1c With Implications for Glycemic Status in U.S. Hispanics/Latinos.

Publications

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A<sub>1c</sub> With Implications for Glycemic Status in U.S. Hispanics/Latinos.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A_1c With Implications for Glycemic Status in U.S. Hispanics/Latinos.