Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

TY - JOUR

T1 - Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

AU - Verhoeven, Virginie J M

AU - Hysi, Pirro G

AU - Saw, Seang-Mei

AU - Vitart, Veronique

AU - Mirshahi, Alireza

AU - Guggenheim, Jeremy A

AU - Cotch, Mary Frances

AU - Yamashiro, Kenji

AU - Baird, Paul N

AU - Mackey, David A

AU - Wojciechowski, Robert

AU - Ikram, M Kamran

AU - Hewitt, Alex W

AU - Duggal, Priya

AU - Janmahasatian, Sarayut

AU - Khor, Chiea-Chuen

AU - Fan, Qiao

AU - Zhou, Xin

AU - Young, Terri L

AU - Tai, E-Shyong

AU - Goh, Liang-Kee

AU - Li, Yi-Ju

AU - Aung, Tin

AU - Vithana, Eranga

AU - Teo, Yik-Ying

AU - Tay, Wanting

AU - Sim, Xueling

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Wright, Alan F

AU - Polasek, Ozren

AU - Campbell, Harry

AU - Wilson, James F

AU - Fleck, Brian W

AU - Nakata, Isao

AU - Yoshimura, Nagahisa

AU - Yamada, Ryo

AU - Matsuda, Fumihiko

AU - Ohno-Matsui, Kyoko

AU - Nag, Abhishek

AU - McMahon, George

AU - St Pourcain, Beate

AU - Lu, Yi

AU - Rahi, Jugnoo S

AU - Cumberland, Phillippa M

AU - Bhattacharya, Shomi

AU - Simpson, Claire L

AU - Atwood, Larry D

AU - Li, Xiaohui

AU - Raffel, Leslie J

AU - Murgia, Federico

AU - Portas, Laura

AU - Despriet, Dominiek D G

AU - van Koolwijk, Leonieke M E

AU - Wolfram, Christian

AU - Lackner, Karl J

AU - Tönjes, Anke

AU - Mägi, Reedik

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Esko, Tõnu

AU - Metspalu, Andres

AU - Rantanen, Taina

AU - Pärssinen, Olavi

AU - Klein, Barbara E

AU - Meitinger, Thomas

AU - Spector, Timothy D

AU - Oostra, Ben A

AU - Smith, Albert V

AU - de Jong, Paulus T V M

AU - Hofman, Albert

AU - Amin, Najaf

AU - Karssen, Lennart C

AU - Rivadeneira, Fernando

AU - Vingerling, Johannes R

AU - Eiríksdóttir, Guðný

AU - Gudnason, Vilmundur

AU - Döring, Angela

AU - Bettecken, Thomas

AU - Uitterlinden, André G

AU - Williams, Cathy

AU - Zeller, Tanja

AU - Castagné, Raphaële

AU - Oexle, Konrad

AU - van Duijn, Cornelia M

AU - Iyengar, Sudha K

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Höhn, René

AU - Pfeiffer, Norbert

AU - Bailey-Wilson, Joan E

AU - Stambolian, Dwight

AU - Wong, Tien-Yin

AU - Hammond, Christopher J

AU - Klaver, Caroline C W

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - Alleles

KW - Chromosomes, Human, Pair 15

KW - Humans

KW - Myopia/genetics

KW - Phenotype

KW - Polymorphism, Single Nucleotide

U2 - 10.1007/s00439-012-1176-0

DO - 10.1007/s00439-012-1176-0

M3 - SCORING: Journal article

C2 - 22665138

VL - 131

SP - 1467

EP - 1480

JO - HUM GENET

JF - HUM GENET

SN - 0340-6717

IS - 9

ER -