Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma.
We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10⁻¹⁰). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.
Thorleifsson
Gudmar
G
deCODE genetics Inc, Reykjavik, Iceland. gudmar.thorleifsson@decode.is
Walters
G Bragi
GB
Hewitt
Alex W
AW
Masson
Gisli
G
Helgason
Agnar
A
DeWan
Andrew
A
Sigurdsson
Asgeir
A
Jonasdottir
Adalbjorg
A
Gudjonsson
Sigurjon A
SA
Magnusson
Kristinn P
KP
Stefansson
Hreinn
H
Lam
Dennis S C
DS
Tam
Pancy O S
PO
Gudmundsdottir
Gudrun J
GJ
Southgate
Laura
L
Burdon
Kathryn P
KP
Gottfredsdottir
Maria Soffia
MS
Aldred
Micheala A
MA
Mitchell
Paul
P
St Clair
David
D
Collier
David A
DA
Tang
Nelson
N
Sveinsson
Orn
O
Macgregor
Stuart
S
Martin
Nicholas G
NG
Cree
Angela J
AJ
Gibson
Jane
J
Macleod
Alex
A
Jacob
Aby
A
Ennis
Sarah
S
Young
Terri L
TL
Chan
Juliana C N
JC
Karwatowski
Wojciech S S
WS
Hammond
Christopher J
CJ
Thordarson
Kristjan
K
Zhang
Mingzhi
M
Wadelius
Claes
C
Lotery
Andrew J
AJ
Trembath
Richard C
RC
Pang
Chi Pui
CP
Hoh
Josephine
J
Craig
Jamie E
JE
Kong
Augustine
A
Mackey
David A
DA
Jonasson
Fridbert
F
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D051243:Caveolin 2 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2