Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.
Ganesh
Santhi K
SK
National Human Genome Research Institute, Division of Intramural Research, Bethesda, MD, USA. ganeshs@mail.nih.gov
Zakai
Neil A
NA
van Rooij
Frank J A
FJ
Soranzo
Nicole
N
Smith
Albert V
AV
Nalls
Michael A
MA
Chen
Ming-Huei
MH
Kottgen
Anna
A
Glazer
Nicole L
NL
Dehghan
Abbas
A
Kuhnel
Brigitte
B
Aspelund
Thor
T
Yang
Qiong
Q
Tanaka
Toshiko
T
Jaffe
Andrew
A
Bis
Joshua C M
JC
Verwoert
Germaine C
GC
Teumer
Alexander
A
Fox
Caroline S
CS
Guralnik
Jack M
JM
Ehret
Georg B
GB
Rice
Kenneth
K
Felix
Janine F
JF
Rendon
Augusto
A
Eiriksdottir
Gudny
G
Levy
Daniel
D
Patel
Kushang V
KV
Boerwinkle
Eric
E
Rotter
Jerome I
JI
Hofman
Albert
A
Sambrook
Jennifer G
JG
Hernandez
Dena G
DG
Zheng
Gang
G
Bandinelli
Stefania
S
Singleton
Andrew B
AB
Coresh
Josef
J
Lumley
Thomas
T
Uitterlinden
André G
AG
Vangils
Janine M
JM
Launer
Lenore J
LJ
Cupples
L Adrienne
LA
Oostra
Ben A
BA
Zwaginga
Jaap-Jan
JJ
Ouwehand
Willem H
WH
Thein
Swee-Lay
SL
Meisinger
Christa
C
Deloukas
Panos
P
Nauck
Matthias
M
Spector
Tim D
TD
Gieger
Christian
C
Gudnason
Vilmundur
V
van Duijn
Cornelia M
CM
Psaty
Bruce M
BM
Ferrucci
Luigi
L
Chakravarti
Aravinda
A
Greinacher
Andreas
A
O'Donnell
Christopher J
CJ
Witteman
Jacqueline C M
JC
Furth
Susan
S
Cushman
Mary
M
Harris
Tamara B
TB
Lin
Jing-Ping
JP
D001794:Blood Pressure / Q000235:genetics*; D002460:Cell Line; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D015870:Gene Expression; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci