TY - JOUR
T1 - A genome-wide association study of optic disc parameters
AU - Ramdas, Wishal D
AU - van Koolwijk, Leonieke M E
AU - Ikram, M Kamran
AU - Jansonius, Nomdo M
AU - de Jong, Paulus T V M
AU - Bergen, Arthur A B
AU - Isaacs, Aaron
AU - Amin, Najaf
AU - Aulchenko, Yurii S
AU - Wolfs, Roger C W
AU - Hofman, Albert
AU - Rivadeneira, Fernando
AU - Oostra, Ben A
AU - Uitterlinden, Andre G
AU - Hysi, Pirro
AU - Hammond, Christopher J
AU - Lemij, Hans G
AU - Vingerling, Johannes R
AU - Klaver, Caroline C W
AU - van Duijn, Cornelia M
PY - 2010/6/10
Y1 - 2010/6/10
N2 - The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19)) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33)) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11)) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10)) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
AB - The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19)) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33)) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11)) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10)) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Female
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Middle Aged
KW - Optic Disk/metabolism
KW - Young Adult
U2 - 10.1371/journal.pgen.1000978
DO - 10.1371/journal.pgen.1000978
M3 - Review article
C2 - 20548946
SN - 1553-7390
VL - 6
SP - e1000978
JO - PLoS Genetics
JF - PLoS Genetics
IS - 6
ER -