Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis
文献类型：期刊论文
| 作者 | Wheeler, Eleanor128; Soranzo, Nicole128; Barroso, Ines128; Leong, Aaron129,130; Porneala, Bianca C.129; Meigs, James B.123,129,130; Florez, Jose C.130; Liu, Ching-Ti131; Hong, Jaeyoung131; Rybin, Denis V.131 |
| 刊名 | PLOS MEDICINE
 |
| 出版日期 | 2017 |
| 卷号 | 14期号:9页码:e1002383 |
| 关键词 | Carassius auratus Selenoprotein T mRNA expression Cadmium Oxidative stress Heat stress |
| ISSN号 | 1549-1676 |
| DOI | 10.1371/journal.pmed.1002383 |
| 文献子类 | Article |
| 英文摘要 | Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods & findings Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses. |
| 学科主题 | General & Internal Medicine |
| WOS关键词 | FASTING PLASMA-GLUCOSE ; GLYCATED HEMOGLOBIN ; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY ; AFRICAN-AMERICANS ; GLYCEMIC TRAITS ; COMPLEX TRAITS ; US POPULATION ; UNITED-STATES ; A(1C) LEVELS ; ASSOCIATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000411970300003 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1147]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.UCL, Inst Cardiovasc Sci, London, England; 2.NHS Blood & Transplant, Oxford, England; 3.Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England; 4.Spanish Biomed Res Ctr Diabet & Assoc Metab Disor, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Madrid, Spain; 5.Univ Med Greifswald, Inst Community Med, Greifswald, Germany; 6.Natl Inst Hlth & Welf THL, Helsinki, Finland; 7.Univ Helsinki, Inst Mol Med, Finland FIMM & Diabet & Obes Res Program, Helsinki, Finland; 8.NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA; 9.Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands; 10.Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, ICIN, Utrecht, Netherlands; |
| 推荐引用方式 GB/T 7714 | Wheeler, Eleanor,Soranzo, Nicole,Barroso, Ines,et al. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis[J]. PLOS MEDICINE,2017,14(9):e1002383. |
| APA | Wheeler, Eleanor.,Soranzo, Nicole.,Barroso, Ines.,Leong, Aaron.,Porneala, Bianca C..,...&,.(2017).Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.PLOS MEDICINE,14(9),e1002383. |
| MLA | Wheeler, Eleanor,et al."Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis".PLOS MEDICINE 14.9(2017):e1002383. |
入库方式： OAI收割
来源：上海营养与健康研究所
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