TY - JOUR
T1 - Replication and characterization of association between ABO SNPs and red blood cell traits by meta-analysis in Europeans
AU - UCLEB Consortium
AU - McLachlan, Stela
AU - Giambartolomei, Claudia
AU - White, Jon
AU - Charoen, Pimphen
AU - Wong, Andrew
AU - Finan, Chris
AU - Engmann, Jorgen
AU - Shah, Tina
AU - Hersch, Micha
AU - Podmore, Clara
AU - Cavadino, Alana
AU - Jefferis, Barbara J.
AU - Dale, Caroline E.
AU - Hypponen, Elina
AU - Morris, Richard W.
AU - Casas, Juan P.
AU - Kumari, Meena
AU - Ben-Shlomo, Yoav
AU - Gaunt, Tom R.
AU - Drenos, Fotios
AU - Langenberg, Claudia
AU - Kuh, Diana
AU - Kivimaki, Mika
AU - Rueedi, Rico
AU - Waeber, Gerard
AU - Hingorani, Aroon D.
AU - Price, Jacqueline F.
AU - Walker, Ann P.
AU - Cooper, Jackie
AU - Day, Ian N.
AU - De Silva, Maneka
AU - Dudbridge, Frank
AU - Fatemifar, Ghazaleh
AU - Garfield, Victoria
AU - Humphries, Steve E.
AU - Lawlor, Debbie A.
AU - Davies, Teri Louise
AU - Plagnol, Vincent
AU - Power, Christine
AU - Shah, Sonia
AU - Sofat, Reecha
AU - Swerdlow, Daniel I.
AU - Talmud, Philippa J.
AU - Whincup, Peter
AU - Whittaker, John C.
AU - Zabaneh, Delilah
N1 - Publisher 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.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84976264664
U2 - 10.1371/journal.pone.0156914
DO - 10.1371/journal.pone.0156914
M3 - Article
C2 - 27280446
AN - SCOPUS:84976264664
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0156914
ER -