Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.
We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
Gretarsdottir
Solveig
S
Population Genomics, deCODE Genetics, Reykjavik, Iceland. solveig.gretarsdottir@decode.is
Baas
Annette F
AF
Thorleifsson
Gudmar
G
Holm
Hilma
H
den Heijer
Martin
M
de Vries
Jean-Paul P M
JP
Kranendonk
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SE
Zeebregts
Clark J A M
CJ
van Sterkenburg
Steven M
SM
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RH
van Rij
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AM
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Michael J A
MJ
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Albert P M
AP
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JP
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Aslaug
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Masson
Gisli
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Sulem
Patrick
P
Saemundsdottir
Jona
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Mouy
Magali
M
Magnusson
Kristinn P
KP
Tromp
Gerard
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Wijmenga
Cisca
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Svati H
SH
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Christopher B
CB
Quyyumi
Arshed A
AA
Vaccarino
Viola
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Patel
Riyaz S
RS
Zafari
A Maziar
AM
Levey
Allan I
AI
Austin
Harland
H
Girelli
Domenico
D
Pignatti
Pier Franco
PF
Olivieri
Oliviero
O
Martinelli
Nicola
N
Malerba
Giovanni
G
Trabetti
Elisabetta
E
Becker
Lewis C
LC
Becker
Diane M
DM
Reilly
Muredach P
MP
Rader
Daniel J
DJ
Mueller
Thomas
T
Dieplinger
Benjamin
B
Haltmayer
Meinhard
M
Urbonavicius
Sigitas
S
Lindblad
Bengt
B
Gottsäter
Anders
A
Gaetani
Eleonora
E
Pola
Roberto
R
Wells
Philip
P
Rodger
Marc
M
Forgie
Melissa
M
Langlois
Nicole
N
Corral
Javier
J
Vicente
Vicente
V
Fontcuberta
Jordi
J
España
Francisco
F
Grarup
Niels
N
Jørgensen
Torben
T
Witte
Daniel R
DR
Hansen
Torben
T
Pedersen
Oluf
O
Aben
Katja K
KK
de Graaf
Jacqueline
J
Holewijn
Suzanne
S
Folkersen
Lasse
L
Franco-Cereceda
Anders
A
Eriksson
Per
P
Collier
David A
DA
Stefansson
Hreinn
H
Steinthorsdottir
Valgerdur
V
Rafnar
Thorunn
T
Valdimarsson
Einar M
EM
Magnadottir
Hulda B
HB
Sveinbjornsdottir
Sigurlaug
S
Olafsson
Isleifur
I
Magnusson
Magnus Karl
MK
Palmason
Robert
R
Haraldsdottir
Vilhelmina
V
Andersen
Karl
K
Onundarson
Pall T
PT
Thorgeirsson
Gudmundur
G
Kiemeney
Lambertus A
LA
Powell
Janet T
JT
Carey
David J
DJ
Kuivaniemi
Helena
H
Lindholt
Jes S
JS
Jones
Gregory T
GT
Kong
Augustine
A
Blankensteijn
Jan D
JD
Matthiasson
Stefan E
SE
Thorsteinsdottir
Unnur
U
Stefansson
Kari
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D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000235:genetics* / Q000401:mortality; D001483:Base Sequence; D004198:Disease Susceptibility / Q000150:complications; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D007055:Iceland; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics; D009426:Netherlands; D016017:Odds Ratio; D012307:Risk Factors; D020703:ras GTPase-Activating Proteins
C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins