Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
Department of Ophthalmology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Virginie J M
VJ
Verhoeven
Pirro G
PG
Hysi
Seang-Mei
SM
Saw
Veronique
V
Vitart
Alireza
A
Mirshahi
Jeremy A
JA
Guggenheim
Mary Frances
MF
Cotch
Kenji
K
Yamashiro
Paul N
PN
Baird
David A
DA
Mackey
Robert
R
Wojciechowski
M Kamran
MK
Ikram
Alex W
AW
Hewitt
Priya
P
Duggal
Sarayut
S
Janmahasatian
Chiea-Chuen
CC
Khor
Qiao
Q
Fan
Xin
X
Zhou
Terri L
TL
Young
E-Shyong
ES
Tai
Liang-Kee
LK
Goh
Yi-Ju
YJ
Li
Tin
T
Aung
Eranga
E
Vithana
Yik-Ying
YY
Teo
Wanting
W
Tay
Xueling
X
Sim
Igor
I
Rudan
Caroline
C
Hayward
Alan F
AF
Wright
Ozren
O
Polasek
Harry
H
Campbell
James F
JF
Wilson
Brian W
BW
Fleck
Isao
I
Nakata
Nagahisa
N
Yoshimura
Ryo
R
Yamada
Fumihiko
F
Matsuda
Kyoko
K
Ohno-Matsui
Abhishek
A
Nag
George
G
McMahon
Beate
B
St Pourcain
Yi
Y
Lu
Jugnoo S
JS
Rahi
Phillippa M
PM
Cumberland
Shomi
S
Bhattacharya
Claire L
CL
Simpson
Larry D
LD
Atwood
Xiaohui
X
Li
Leslie J
LJ
Raffel
Federico
F
Murgia
Laura
L
Portas
Dominiek D G
DD
Despriet
Leonieke M E
LM
van Koolwijk
Christian
C
Wolfram
Karl J
KJ
Lackner
Anke
A
Tönjes
Reedik
R
Mägi
Terho
T
Lehtimäki
Mika
M
Kähönen
Tõnu
T
Esko
Andres
A
Metspalu
Taina
T
Rantanen
Olavi
O
Pärssinen
Barbara E
BE
Klein
Thomas
T
Meitinger
Timothy D
TD
Spector
Ben A
BA
Oostra
Albert V
AV
Smith
Paulus T V M
PT
de Jong
Albert
A
Hofman
Najaf
N
Amin
Lennart C
LC
Karssen
Fernando
F
Rivadeneira
Johannes R
JR
Vingerling
Guðný
G
Eiríksdóttir
Vilmundur
V
Gudnason
Angela
A
Döring
Thomas
T
Bettecken
André G
AG
Uitterlinden
Cathy
C
Williams
Tanja
T
Zeller
Raphaële
R
Castagné
Konrad
K
Oexle
Cornelia M
CM
van Duijn
Sudha K
SK
Iyengar
Paul
P
Mitchell
Jie Jin
JJ
Wang
René
R
Höhn
Norbert
N
Pfeiffer
Joan E
JE
Bailey-Wilson
Dwight
D
Stambolian
Tien-Yin
TY
Wong
Christopher J
CJ
Hammond
Caroline C W
CC
Klaver
D000483:Alleles; D002884:Chromosomes, Human, Pair 15; D006801:Humans; D009216:Myopia / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide