title: Genotype-phenotype analysis of SNPs associated with primary angle closure glaucoma (rs1015213, rs3753841 and rs11024102) and ocular biometry in the EPIC-Norfolk Eye Study.
abstract: OBJECTIVE
  To investigate if the single nucleotide polymorphisms rs3753841, rs1015213 and rs11024102, recently implicated in the development of acute primary angle closure or primary angle closure glaucoma, are associated with ocular biometric characteristics of British adults in the European Prospective Investigation of Cancer-Norfolk eye study.
  
  
  METHODS
  Genotyping data on rs1015213 (between PCMTD1 and ST18), rs11024102 (at PLEKHA7) and rs3753841 (at COL11A1) were available on 3268 participants. Direct genotypic data was available for rs1015213 and rs3753841. Data was imputed for rs11024102. Ocular biometric data was available on 1137 participants who attended the third European Prospective Investigation of Cancer health examination and 988 (87%) of these participants had no previous cataract surgery either eye. Axial length (AL), anterior chamber depth (ACD) and corneal keratometry were measured by using the Zeiss IOLMaster.
  
  
  RESULTS
  Presence of at least one A allele (AG or AA genotype) for rs1015213 was associated with a shallower ACD (-0.07 mm, 95% CI -0.01 to -0.14 mm, p=0.028) after adjusting for age and sex (both p≤0.001). There was no association with AL or corneal keratometry for rs1015213 genotypes. AL, ACD and keratometry were not associated with rs3753841 or rs11024102 genotypes including after adjusting for age and sex.
  
  
  CONCLUSIONS
  This study suggests that primary angle closure glaucoma susceptibility at the PCMTD1-ST18 locus may be partly explained by an association between rs1015213 and ACD in European populations. This effect is equivalent to almost 20% of the SD of the mean ACD of phakic individuals in this cohort. We were not able to identify any association between rs3753841 or rs11024102 and ocular biometry.
authors.affiliation: The NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Day
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Khawaja
authors.forename: Sancy
authors.initials: S
authors.lastname: Low
authors.forename: Shabina
authors.initials: S
authors.lastname: Hayat
authors.forename: Nichola
authors.initials: N
authors.lastname: Dalzell
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Foster
mesh_terms: D000368:Aged; D001699:Biometry / Q000379:methods; D002352:Carrier Proteins / Q000235:genetics*; D024161:Collagen Type XI / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D015812:Glaucoma, Angle-Closure / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: C574182:COL11A1 protein, human; D002352:Carrier Proteins; D024161:Collagen Type XI; C533786:PLEKHA7 protein, human; D012097:Repressor Proteins; C497230:ST18 protein, human; C435725:PCMT1 protein, human; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase
keywords: Anatomy; Angle; Anterior Chamber; Genetics; Glaucoma