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

全基因组关联研究 血糖性 2型糖尿病 生物 遗传学 遗传关联 糖化血红素 糖尿病 医学 内科学 基因型 单核苷酸多态性 内分泌学 基因
作者
Eleanor Wheeler,Aaron Leong,Yongmei Liu,Marie‐France Hivert,Rona J. Strawbridge,Clara Podmore,Man Li,Jie Yao,Xueling Sim,Jaeyoung Hong,Audrey Y. Chu,Weihua Zhang,Xu Wang,Peng Chen,Nisa M. Maruthur,Bianca Porneala,Stephen J. Sharp,Yucheng Jia,Edmond K. Kabagambe,Li-Ching Chang,Wei‐Min Chen,Cathy E. Elks,Daniel S. Evans,Qiao Fan,Franco Giulianini,Min Jin Go,Jouke‐Jan Hottenga,Yao Hu,Anne Jackson,Stavroula Kanoni,Young Jin Kim,Marcus E. Kleber,Claes Ladenvall,Cécile Lecœur,Sing-Hui Lim,Yingchang Lu,Anubha Mahajan,Carola Marzi,Mike A. Nalls,Pau Navarro,Ilja M. Nolte,Lynda M. Rose,Denis Rybin,Serena Sanna,Yuan Shi,Daniel O. Stram,Fumihiko Takeuchi,Shu Pei Tan,Peter J. van der Most,Jana V. van Vliet‐Ostaptchouk,Andrew Wong,Loïc Yengo,Wanting Zhao,Anuj Goel,María Teresa Martínez Larrad,Dörte Radke,Perttu Salo,Toshiko Tanaka,Erik P.A. van Iperen,Gonçalo R. Abecasis,Saima Afaq,Behrooz Z. Alizadeh,Alain G. Bertoni,Amélie Bonnefond,Yvonne Böttcher,Erwin P. Böttinger,Harry Campbell,Olga D. Carlson,Chien-Hsiun Chen,Yoon Shin Cho,W. Timothy Garvey,Christian Gieger,Mark O. Goodarzi,Harald Grallert,Anders Hamsten,Catharina A. Hartman,Christian Herder,Chao A. Hsiung,Jie Huang,Michiya Igase,Masato Isono,Tomohiro Katsuya,Chiea Chuen Khor,Wieland Kieß,Katsuhiko Kohara,Péter Kovács,Juyoung Lee,Wen‐Jane Lee,Benjamin Lehne,Huaixing Li,Jing Liu,Stéphane Lobbens,Jian’an Luan,Valeriya Lyssenko,Thomas Meitinger,Tetsuro Miki,Iva Miljkovic,Sanghoon Moon,Antonella Mulas,Gabriele Müller,Martina Müller‐Nurasyid,Ramaiah Nagaraja,Matthias Nauck,James S. Pankow,Ozren Polašek,Inga Prokopenko,Paula S. Ramos,Laura J. Rasmussen‐Torvik,Wolfgang Rathmann,Stephen S. Rich,Neil R. Robertson,Michael Roden,Ronan Roussel,Igor Rudan,Robert A. Scott,William R. Scott,Bengt Sennblad,David S. Siscovick,Konstantin Strauch,Liang Sun,Morris A. Swertz,Salman M. Tajuddin,Kent D. Taylor,Yik‐Ying Teo,Yih‐Chung Tham,Anke Tönjes,Nicholas J. Wareham,Gonneke Willemsen,Tom Wilsgaard,Aroon D. Hingorani,Josephine Egan,Luigi Ferrucci,G. Kees Hovingh,Antti Jula,Mika Kivimäki,Meena Kumari,Inger Njølstad,Nicholette D. Palmer,Manuel Serrano‐Ríos,Michael Stümvoll,Hugh Watkins,Tin Aung,Matthias Blüher,Michael Boehnke,Dorret I. Boomsma,Stefan R. Bornstein,John C. Chambers,Daniel I. Chasman,Yii‐Der Ida Chen,Yduan-Tsong Chen,Ching‐Yu Cheng,Francesco Cucca,Eco J. C. de Geus,Panos Deloukas,Michele K. Evans,Myriam Fornage,Yechiel Friedlander,Philippe Froguel,Leif Groop,Myron D. Gross,Tamara B. Harris,Caroline Hayward,Chew‐Kiat Heng,Erik Ingelsson,Norihiro Kato,Bong-Jo Kim,Woon-Puay Koh,Jaspal S. Kooner,Antje Körner,Diana Kuh,Johanna Kuusisto,Markku Laakso,Lin Xu,Yongmei Liu,Ruth J. F. Loos,Patrik K. E. Magnusson,Winfried März,Mark I. McCarthy,Albertine J. Oldehinkel,Ken K. Ong,Nancy L. Pedersen,Mark A. Pereira,Annette Peters,Paul M. Ridker,Charumathi Sabanayagam,Michèle M. Sale,Danish Saleheen,Juha Saltevo,Peter E. H. Schwarz,Wayne H.-H. Sheu,Harold Snieder,Timothy D. Spector,Yasuharu Tabara,Jaakko Tuomilehto,Rob M. van Dam,James G. Wilson,James F. Wilson,Bruce H. R. Wolffenbuttel,Tien Yin Wong,Zhenhua Wu,Jian‐Min Yuan,Alan B. Zonderman,Nicole Soranzo,Xiuqing Guo,David J. Roberts,José C. Florez,Robert Sladek,Josée Dupuis,Andrew P. Morris,E. Shyong Tai,Elizabeth Selvin,Jerome I. Rotter,Claudia Langenberg,Inês Barroso,James B. Meigs
出处
期刊:PLOS Medicine [Public Library of Science]
卷期号:14 (9): e1002383-e1002383 被引量:383
标识
DOI:10.1371/journal.pmed.1002383
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 × 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% CI 0.55–0.74) of African American adults with T2D to 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.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
romeo发布了新的文献求助10
3秒前
妖孽宇完成签到,获得积分10
5秒前
简简单单完成签到,获得积分10
5秒前
550190946发布了新的文献求助10
5秒前
7秒前
111完成签到,获得积分10
7秒前
zhubin完成签到 ,获得积分10
7秒前
9秒前
田南松发布了新的文献求助10
12秒前
搬砖美少女完成签到,获得积分10
12秒前
nn发布了新的文献求助10
13秒前
7ohnny完成签到,获得积分10
14秒前
apckkk完成签到 ,获得积分10
16秒前
深情安青应助550190946采纳,获得10
17秒前
18秒前
19秒前
jbq完成签到 ,获得积分20
19秒前
YM完成签到,获得积分10
21秒前
生动柔发布了新的文献求助10
21秒前
大旭完成签到 ,获得积分10
22秒前
Fn完成签到 ,获得积分10
24秒前
zero完成签到,获得积分10
26秒前
瘦瘦谷兰完成签到,获得积分10
26秒前
zcz完成签到 ,获得积分10
27秒前
白嘉乐完成签到,获得积分10
28秒前
考研小白完成签到,获得积分10
28秒前
高妍纯完成签到 ,获得积分10
30秒前
32秒前
风中的丝袜完成签到,获得积分10
32秒前
赵赵完成签到,获得积分10
35秒前
35秒前
shiizii应助科研通管家采纳,获得10
36秒前
xuzj应助科研通管家采纳,获得10
36秒前
Mars应助科研通管家采纳,获得30
36秒前
Hello应助科研通管家采纳,获得10
36秒前
叶梓轩完成签到 ,获得积分10
36秒前
上官若男应助科研通管家采纳,获得10
36秒前
36秒前
36秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038201
求助须知:如何正确求助?哪些是违规求助? 3575940
关于积分的说明 11373987
捐赠科研通 3305747
什么是DOI,文献DOI怎么找? 1819274
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022