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.
National Human Genome Research Institute, Division of Intramural Research, Bethesda, MD, USA. ganeshs@mail.nih.gov
Santhi K
SK
Ganesh
Neil A
NA
Zakai
Frank J A
FJ
van Rooij
Nicole
N
Soranzo
Albert V
AV
Smith
Michael A
MA
Nalls
Ming-Huei
MH
Chen
Anna
A
Kottgen
Nicole L
NL
Glazer
Abbas
A
Dehghan
Brigitte
B
Kuhnel
Thor
T
Aspelund
Qiong
Q
Yang
Toshiko
T
Tanaka
Andrew
A
Jaffe
Joshua C M
JC
Bis
Germaine C
GC
Verwoert
Alexander
A
Teumer
Caroline S
CS
Fox
Jack M
JM
Guralnik
Georg B
GB
Ehret
Kenneth
K
Rice
Janine F
JF
Felix
Augusto
A
Rendon
Gudny
G
Eiriksdottir
Daniel
D
Levy
Kushang V
KV
Patel
Eric
E
Boerwinkle
Jerome I
JI
Rotter
Albert
A
Hofman
Jennifer G
JG
Sambrook
Dena G
DG
Hernandez
Gang
G
Zheng
Stefania
S
Bandinelli
Andrew B
AB
Singleton
Josef
J
Coresh
Thomas
T
Lumley
André G
AG
Uitterlinden
Janine M
JM
Vangils
Lenore J
LJ
Launer
L Adrienne
LA
Cupples
Ben A
BA
Oostra
Jaap-Jan
JJ
Zwaginga
Willem H
WH
Ouwehand
Swee-Lay
SL
Thein
Christa
C
Meisinger
Panos
P
Deloukas
Matthias
M
Nauck
Tim D
TD
Spector
Christian
C
Gieger
Vilmundur
V
Gudnason
Cornelia M
CM
van Duijn
Bruce M
BM
Psaty
Luigi
L
Ferrucci
Aravinda
A
Chakravarti
Andreas
A
Greinacher
Christopher J
CJ
O'Donnell
Jacqueline C M
JC
Witteman
Susan
S
Furth
Mary
M
Cushman
Tamara B
TB
Harris
Jing-Ping
JP
Lin
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