title: Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area.
abstract: Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tay
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Zheng
authors.forename: Raghavan
authors.initials: R
authors.lastname: Lavanya
authors.forename: Renyi
authors.initials: R
authors.lastname: Wu
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: Martin
authors.initials: M
authors.lastname: Hibberd
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Nomdo M
authors.initials: NM
authors.lastname: Jansonius
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000378:metabolism; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000737:chemistry* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053468:CARD Signaling Adaptor Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C456975:ATOH7 protein, human; C430880:CARD10 protein, human; C071736:betaglycan