title: A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma.
abstract: Primary open angle glaucoma (POAG) is one of leading causes of adult blindness worldwide. To identify genetic variants associated with susceptibility to POAG, we conducted a genome-wide association study (GWAS) using 1394 cases and 6599 controls. Subsequently, we analyzed 33 single nucleotide polymorphisms (SNPs) which showed suggestive association (P < 1 × 10(-4)) by GWAS, using an additional set of 1802 cases and 7212 controls. In addition to confirmation of the association of the chromosome 9p21 locus [rs1063192, P= 5.2 × 10(-11), odds ratio (OR) = 0.75], and 14q23 (rs10483727, P = 9.49 × 10(-8), OR = 0.79) with POAG in Caucasians reported recently, we identified a suggestive-associated locus on 2q21 (rs7588567, P = 3.89 × 10(-7), OR = 0.85). For these described SNPs, minor alleles are suspected to have a protective effect from the disease. An linkage disequilibrium block containing rs10483727 includes the SIX6 gene that was implicated to have a critical role in eye development, and genes in both represented loci (SIX6 on chromosome 14q23, and CDKN2A-CDKN2B on chromosome 9p21) are known to be expressed in human ocular tissues, including the retina. Our GWAS results should contribute to better insight into the genetic basis of POAG.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Wael
authors.initials: W
authors.lastname: Osman
authors.forename: Siew-Kee
authors.initials: SK
authors.lastname: Low
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018398:Homeodomain Proteins; C491945:SIX6 protein, human; D015534:Trans-Activators