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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.

Eleanor Wheeler | Aaron Leong | Ching-Ti 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 C 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 U Jackson | Stavroula Kanoni | Young Jin Kim | Marcus E Kleber | Claes Ladenvall | Cecile Lecoeur | Sing-Hui Lim | Yingchang Lu | Anubha Mahajan | Carola Marzi | Mike A Nalls | Pau Navarro | Ilja M Nolte | Lynda M Rose | Denis V 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 | Loic Yengo | Wanting Zhao | Anuj Goel | Maria Teresa Martinez Larrad | Dörte Radke | Perttu Salo | Toshiko Tanaka | Erik P A van Iperen | Goncalo Abecasis | Saima Afaq | Behrooz Z Alizadeh | Alain G Bertoni | Amelie Bonnefond | Yvonne Böttcher | Erwin P Bottinger | 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 Agnes Hsiung | Jie Huang | Michiya Igase | Masato Isono | Tomohiro Katsuya | Chiea-Chuen Khor | Wieland Kiess | Katsuhiko Kohara | Peter Kovacs | Juyoung Lee | Wen-Jane Lee | Benjamin Lehne | Huaixing Li | Jianjun Liu | Stephane 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 Polasek | Inga Prokopenko | Paula S Ramos | Laura 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 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 | EPIC-CVD Consortium | EPIC-InterAct Consortium | Lifelines Cohort Study | Josephine Egan | Luigi Ferrucci | G Kees Hovingh | Antti Jula | Mika Kivimaki | Meena Kumari | Inger Njølstad | Colin N A Palmer | Manuel Serrano Ríos | Michael Stumvoll | 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 | Xu Lin | 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 | Michele Sale | Danish Saleheen | Juha Saltevo | Peter Eh 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 | Jer-Yuarn Wu | Jian-Min Yuan | Alan B Zonderman | Nicole Soranzo | Xiuqing Guo | David J Roberts | Jose C Florez | Robert Sladek | Josée Dupuis | Andrew P Morris | E-Shyong Tai | Elizabeth Selvin | Jerome I Rotter | Claudia Langenberg | Inês Barroso | James B Meigs
PLoS medicine | 2017

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.

Pubmed ID: 28898252 RIS Download

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK106236
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK089174
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12015/1
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK079626
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000124
  • Agency: NIH HHS, United States
    Id: S10 OD018522
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL105756
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12015/2
  • Agency: NIDDK NIH HHS, United States
    Id: K24 DK106414
  • Agency: Medical Research Council, United Kingdom
    Id: G0601261
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020572
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001881
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM115428
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K013351/1
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG007417
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063491
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12019/1
  • Agency: NIDDK NIH HHS, United States
    Id: K24 DK080140
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/14/5/30893
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_U127561128
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020541
  • Agency: NCI NIH HHS, United States
    Id: UM1 CA182913
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K002414/1
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK078616
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK062370
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/10/12/28456

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This is a list of tools and resources that we have found mentioned in this publication.


METAL (tool)

RRID:SCR_002013

Software application designed to facilitate meta-analysis of large datasets (such as several whole genome scans) in a convenient, rapid and memory efficient manner. (entry from Genetic Analysis Software)

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Jackson Heart Study (tool)

RRID:SCR_009902

The JHS is the largest single-site longitudinal, population-based, cohort study of 5,302 persons initiated in the fall of 2000 to prospectively investigate the determinants of CVD among African Americans in the Jackson, MS metropolitan statistical area. The JHS investigates the various genotype and phenotype factors that affect high blood pressure, heart disease, strokes, diabetes and other important diseases in African Americans. The primary objective of the Jackson Heart Study is to investigate the causes of cardiovascular disease (CVD) in African Americans to learn how to best prevent this group of diseases in the future. More specific objectives include: 1. Identification of factors, which influence the development, and worsening of CVD in African Americans, with an emphasis on manifestations related to high blood pressure (such as remodeling of the left ventricle of the heart, coronary artery disease, heart failure, stroke and disorders affecting the blood vessels of the kidney). 2. Building research capabilities in minority institutions at the undergraduate and graduate level by developing partnerships between minority and majority institutions and enhancing participation of minority investigators in large-scale epidemiologic studies. 3. Attracting minority students to and preparing them for careers in health sciences.

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National Glycohemoglobin Standardization Program (tool)

RRID:SCR_015885

Project that aims to standardize Hemoglobin A1c test results to those of the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) which established the direct relationships between HbA1c levels and outcome risks in patients with diabetes.

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