PMID- 27280446
OWN - NLM
STAT- MEDLINE
DCOM- 20170727
LR  - 20220129
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 6
DP  - 2016
TI  - Replication and Characterization of Association between ABO SNPs and Red Blood 
      Cell Traits by Meta-Analysis in Europeans.
PG  - e0156914
LID - 10.1371/journal.pone.0156914 [doi]
LID - e0156914
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.
FAU - McLachlan, Stela
AU  - McLachlan S
AD  - Centre for Population Health Sciences, Usher Institute of Population Health 
      Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.
FAU - Giambartolomei, Claudia
AU  - Giambartolomei C
AD  - Department of Psychiatry, Icahn Institute for Genomics and Multiscale Biology, 
      Icahn School of Medicine at Mount Sinai, The Leon and Norma Hess Center for 
      Science and Medicine, New York, New York, United States of America.
FAU - White, Jon
AU  - White J
AUID- ORCID: 0000-0003-2666-561X
AD  - University College London Genetics Institute, Department of Genetics, Environment 
      and Evolution, London, United Kingdom.
FAU - Charoen, Pimphen
AU  - Charoen P
AD  - Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and 
      Population Health, London School of Hygiene and Tropical Medicine, London, United 
      Kingdom.
AD  - Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 
      Bangkok, Thailand.
FAU - Wong, Andrew
AU  - Wong A
AD  - MRC Unit for Lifelong Health and Ageing at UCL, London, United Kingdom.
FAU - Finan, Chris
AU  - Finan C
AD  - Institute of Cardiovascular Science, University College London, London, United 
      Kingdom.
FAU - Engmann, Jorgen
AU  - Engmann J
AD  - Genetic Epidemiology Group, Institute of Cardiovascular Science, University 
      College London, London, United Kingdom.
AD  - Farr Institute of Health Informatics Research, Department of Epidemiology & 
      Public Health, University College London, London, United Kingdom.
FAU - Shah, Tina
AU  - Shah T
AD  - Genetic Epidemiology Group, Institute of Cardiovascular Science, University 
      College London, London, United Kingdom.
FAU - Hersch, Micha
AU  - Hersch M
AD  - Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
AD  - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Podmore, Clara
AU  - Podmore C
AUID- ORCID: 0000-0002-2452-8067
AD  - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, 
      Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United 
      Kingdom.
FAU - Cavadino, Alana
AU  - Cavadino A
AD  - Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive 
      Medicine, Queen Mary University of London, London, United Kingdom.
AD  - Population, Policy and Practice, UCL Institute of Child Health, University 
      College London, London, United Kingdom.
FAU - Jefferis, Barbara J
AU  - Jefferis BJ
AD  - Department of Primary Care & Population Health, UCL Institute of Epidemiology & 
      Health Care, University College London, London, United Kingdom.
FAU - Dale, Caroline E
AU  - Dale CE
AD  - Farr Institute of Health Informatics Research, Department of Epidemiology & 
      Public Health, University College London, London, United Kingdom.
FAU - Hypponen, Elina
AU  - Hypponen E
AD  - Population, Policy and Practice, UCL Institute of Child Health, University 
      College London, London, United Kingdom.
AD  - Centre for Population Health Research, School of Health Sciences and Sansom 
      Institute of Health Research, University of South Australia, Adelaide, Australia.
AD  - South Australian Health and Medical Research Institute, Adelaide, Australia.
FAU - Morris, Richard W
AU  - Morris RW
AD  - Department of Primary Care & Population Health, UCL Institute of Epidemiology & 
      Health Care, University College London, London, United Kingdom.
AD  - School of Social and Community Medicine, University of Bristol, Bristol, United 
      Kingdom.
FAU - Casas, Juan P
AU  - Casas JP
AD  - Institute of Health Informatics, University College London, London, United 
      Kingdom.
FAU - Kumari, Meena
AU  - Kumari M
AD  - Institute for Social and Economic Research, University of Essex, Colchester, 
      United Kingdom.
AD  - Department of Epidemiology & Public Health, UCL Institute of Epidemiology & 
      Health Care, University College London, London, United Kingdom.
FAU - Ben-Shlomo, Yoav
AU  - Ben-Shlomo Y
AD  - School of Social and Community Medicine, University of Bristol, Bristol, United 
      Kingdom.
FAU - Gaunt, Tom R
AU  - Gaunt TR
AD  - MRC Integrative Epidemiology Unit, School of Social and Community Medicine, 
      University of Bristol, Bristol, United Kingdom.
FAU - Drenos, Fotios
AU  - Drenos F
AD  - MRC Integrative Epidemiology Unit, School of Social and Community Medicine, 
      University of Bristol, Bristol, United Kingdom.
AD  - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, 
      University College London, London, United Kingdom.
FAU - Langenberg, Claudia
AU  - Langenberg C
AD  - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, 
      Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United 
      Kingdom.
AD  - Institute of Health Informatics, University College London, London, United 
      Kingdom.
FAU - Kuh, Diana
AU  - Kuh D
AD  - MRC Unit for Lifelong Health and Ageing at UCL, London, United Kingdom.
FAU - Kivimaki, Mika
AU  - Kivimaki M
AD  - Department of Epidemiology & Public Health, UCL Institute of Epidemiology & 
      Health Care, University College London, London, United Kingdom.
FAU - Rueedi, Rico
AU  - Rueedi R
AD  - Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
AD  - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Waeber, Gerard
AU  - Waeber G
AD  - Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois and 
      University of Lausanne, Lausanne, Switzerland.
FAU - Hingorani, Aroon D
AU  - Hingorani AD
AD  - Institute of Cardiovascular Science, University College London, London, United 
      Kingdom.
AD  - Farr Institute of Health Informatics Research, Department of Epidemiology & 
      Public Health, University College London, London, United Kingdom.
FAU - Price, Jacqueline F
AU  - Price JF
AD  - Centre for Population Health Sciences, Usher Institute of Population Health 
      Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.
FAU - Walker, Ann P
AU  - Walker AP
AUID- ORCID: 0000-0002-8485-3494
AD  - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, 
      University College London, London, United Kingdom.
CN  - UCLEB Consortium
LA  - eng
GR  - RG/08/013/25942/BHF_/British Heart Foundation/United Kingdom
GR  - MC_UU_12015/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/K006584/1/MRC_/Medical Research Council/United Kingdom
GR  - G1001799/MRC_/Medical Research Council/United Kingdom
GR  - G0000934/MRC_/Medical Research Council/United Kingdom
GR  - RG/13/2/30098/BHF_/British Heart Foundation/United Kingdom
GR  - MC_UU_12019/1/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12013/5/MRC_/Medical Research Council/United Kingdom
GR  - PG/13/66/30442/BHF_/British Heart Foundation/United Kingdom
GR  - RG/10/12/28456/BHF_/British Heart Foundation/United Kingdom
GR  - R01 AG013196/AG/NIA NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
GR  - 10/0003985/DUK_/Diabetes UK/United Kingdom
GR  - MR/K013351/1/MRC_/Medical Research Council/United Kingdom
GR  - RG/07/008/23674/BHF_/British Heart Foundation/United Kingdom
GR  - R01 HL036310/HL/NHLBI NIH HHS/United States
GR  - K013351/MRC_/Medical Research Council/United Kingdom
GR  - RG/13/16/30528/BHF_/British Heart Foundation/United Kingdom
GR  - G0500877/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20160609
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ABO Blood-Group System)
SB  - IM
EIN - PLoS One. 2018 Feb 23;13(2):e0193627. PMID: 29474477
MH  - ABO Blood-Group System/*genetics
MH  - DNA Replication/*genetics
MH  - Erythrocytes/*physiology
MH  - Ethnicity
MH  - Europe
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Quantitative Trait Loci/*genetics
PMC - PMC4900668
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/06/10 06:00
MHDA- 2017/07/28 06:00
PMCR- 2016/06/09
CRDT- 2016/06/10 06:00
PHST- 2016/02/29 00:00 [received]
PHST- 2016/05/20 00:00 [accepted]
PHST- 2016/06/10 06:00 [entrez]
PHST- 2016/06/10 06:00 [pubmed]
PHST- 2017/07/28 06:00 [medline]
PHST- 2016/06/09 00:00 [pmc-release]
AID - PONE-D-16-07914 [pii]
AID - 10.1371/journal.pone.0156914 [doi]
PST - epublish
SO  - PLoS One. 2016 Jun 9;11(6):e0156914. doi: 10.1371/journal.pone.0156914. 
      eCollection 2016.