title: Collagen-related genes influence the glaucoma risk factor, central corneal thickness.
abstract: Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
authors.affiliation: Singapore Eye Research Institute, Singapore. eranga.n.v@seri.com.sg
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tay
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Raghavan
authors.initials: R
authors.lastname: Lavanya
authors.forename: Renyi
authors.initials: R
authors.lastname: Wu
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Zheng
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: Liang Kee
authors.initials: LK
authors.lastname: Goh
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D003094:Collagen / Q000235:genetics*; D024102:Collagen Type VIII / Q000235:genetics; D003315:Cornea / Q000473:pathology*; D005260:Female; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors; D012846:Singapore
chemical_list: C443712:COL8A2 protein, human; D024102:Collagen Type VIII; D003094:Collagen