A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
Soranzo
Nicole
N
Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. ns6@sanger.ac.uk
Spector
Tim D
TD
Mangino
Massimo
M
Kühnel
Brigitte
B
Rendon
Augusto
A
Teumer
Alexander
A
Willenborg
Christina
C
Wright
Benjamin
B
Chen
Li
L
Li
Mingyao
M
Salo
Perttu
P
Voight
Benjamin F
BF
Burns
Philippa
P
Laskowski
Roman A
RA
Xue
Yali
Y
Menzel
Stephan
S
Altshuler
David
D
Bradley
John R
JR
Bumpstead
Suzannah
S
Burnett
Mary-Susan
MS
Devaney
Joseph
J
Döring
Angela
A
Elosua
Roberto
R
Epstein
Stephen E
SE
Erber
Wendy
W
Falchi
Mario
M
Garner
Stephen F
SF
Ghori
Mohammed J R
MJ
Goodall
Alison H
AH
Gwilliam
Rhian
R
Hakonarson
Hakon H
HH
Hall
Alistair S
AS
Hammond
Naomi
N
Hengstenberg
Christian
C
Illig
Thomas
T
König
Inke R
IR
Knouff
Christopher W
CW
McPherson
Ruth
R
Melander
Olle
O
Mooser
Vincent
V
Nauck
Matthias
M
Nieminen
Markku S
MS
O'Donnell
Christopher J
CJ
Peltonen
Leena
L
Potter
Simon C
SC
Prokisch
Holger
H
Rader
Daniel J
DJ
Rice
Catherine M
CM
Roberts
Robert
R
Salomaa
Veikko
V
Sambrook
Jennifer
J
Schreiber
Stefan
S
Schunkert
Heribert
H
Schwartz
Stephen M
SM
Serbanovic-Canic
Jovana
J
Sinisalo
Juha
J
Siscovick
David S
DS
Stark
Klaus
K
Surakka
Ida
I
Stephens
Jonathan
J
Thompson
John R
JR
Völker
Uwe
U
Völzke
Henry
H
Watkins
Nicholas A
NA
Wells
George A
GA
Wichmann
H-Erich
HE
Van Heel
David A
DA
Tyler-Smith
Chris
C
Thein
Swee Lay
SL
Kathiresan
Sekar
S
Perola
Markus
M
Reilly
Muredach P
MP
Stewart
Alexandre F R
AF
Erdmann
Jeanette
J
Samani
Nilesh J
NJ
Meisinger
Christa
C
Greinacher
Andreas
A
Deloukas
Panos
P
Ouwehand
Willem H
WH
Gieger
Christian
C
D001772:Blood Cell Count; D001773:Blood Cells / Q000166:cytology; D002881:Chromosomes, Human, Pair 12; D003324:Coronary Artery Disease / Q000235:genetics; D005819:Genetic Markers; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
D005819:Genetic Markers