Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102068
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Type: Journal article
Title: Replication and characterization of association between ABO SNPs and red blood cell traits by meta-analysis in Europeans
Author: McLachlan, S.
Giambartolomei, C.
White, J.
Charoen, P.
Wong, A.
Finan, C.
Engmann, J.
Shah, T.
Hersch, M.
Podmore, C.
Cavadino, A.
Jefferis, B.
Dale, C.
Hypponen, E.
Morris, R.
Casas, J.
Kumari, M.
Ben-Shlomo, Y.
Gaunt, T.
Drenos, F.
et al.
Citation: PLoS One, 2016; 11(6):e0156914-1-e0156914-18
Publisher: Public Library of Science
Issue Date: 2016
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Stela McLachlan, Claudia Giambartolomei, Jon White, Pimphen Charoen, Andrew Wong, Chris Finan, Jorgen Engmann, Tina Shah, Micha Hersch, Clara Podmore, Alana Cavadino, Barbara J. Jefferis, Caroline E. Dale, Elina Hypponen, Richard W. Morris, Juan P. Casas, Meena Kumari, Yoav Ben-Shlomo, Tom R. Gaunt, Fotios Drenos, Claudia Langenberg, Diana Kuh, Mika Kivimaki, Rico Rueedi, Gerard Waeber, Aroon D. Hingorani, Jacqueline F. Price, Ann P. Walker, UCLEB Consortium
Abstract: Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits-hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)-in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.
Keywords: UCLEB Consortium
Description: Published: June 9, 2016
Rights: Copyright: © 2016 McLachlan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030050606
DOI: 10.1371/journal.pone.0156914
Appears in Collections:Medicine publications

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