Replication and characterization of association between ABO SNPs and red blood cell traits by meta-analysis in Europeans

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 DrenosClaudia Langenberg, Diana Kuh, Mika Kivimaki, Rico Rueedi, Gerard Waeber, Aroon D. Hingorani, Jacqueline F. Price, Ann P. Walker, Jackie Cooper, Ian N. Day, Maneka De Silva, Frank Dudbridge, Ghazaleh Fatemifar, Victoria Garfield, Steve E. Humphries, Debbie A. Lawlor, Teri Louise Davies, Vincent Plagnol, Christine Power, Sonia Shah, Reecha Sofat, Daniel I. Swerdlow, Philippa J. Talmud, Peter Whincup, John C. Whittaker, Delilah Zabaneh, UCLEB Consortium

Research output: Contribution to journalArticle

8 Citations (Scopus)


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.

Original languageEnglish
Article numbere0156914
JournalPloS one
Issue number6
Publication statusPublished - 1 Jun 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this