title: Common mechanisms underlying refractive error identified in functional analysis of gene lists from genome-wide association study results in 2 European British cohorts.
abstract: OBJECTIVE
  To date, relatively few genes responsible for a fraction of heritability have been identified by means of large genetic association studies of refractive error.
  
  
  OBJECTIVE
  To explore the genetic mechanisms that lead to refractive error in the general population.
  
  
  METHODS
  Genome-wide association studies were carried out in 2 British population-based independent cohorts (N = 5928 participants) to identify genes moderately associated with refractive error.
  
  
  METHODS
  Enrichment analyses were used to identify sets of genes overrepresented in both cohorts. Enriched groups of genes were compared between both participating cohorts as a further measure against random noise.
  
  
  RESULTS
  Groups of genes enriched at highly significant statistical levels were remarkably consistent in both cohorts. In particular, these results indicated that plasma membrane (P = 7.64 × 10⁻³⁰), cell-cell adhesion (P = 2.42 × 10⁻¹⁸), synaptic transmission (P = 2.70 × 10⁻¹⁴), calcium ion binding (P = 3.55 × 10⁻¹⁵), and cation channel activity (P = 2.77 × 10⁻¹⁴) were significantly overrepresented in relation to refractive error.
  
  
  CONCLUSIONS
  These findings provide evidence that development of refractive error in the general population is related to the intensity of photosignal transduced from the retina, which may have implications for future interventions to minimize this disorder. Pathways connected to the procession of the nerve impulse are major mechanisms involved in the development of refractive error in populations of European origin.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, England.
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.affiliation: Department of Ophthalmology, King's College London, London, England3Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, England.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Mahroo
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, England.
authors.forename: Phillippa
authors.initials: P
authors.lastname: Cumberland
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Wojciechowski
authors.affiliation: Department of Ophthalmology, King's College London, London, England.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Williams
authors.affiliation: Center for Human Genetics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.affiliation: Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, England.
authors.forename: Jugnoo S
authors.initials: JS
authors.lastname: Rahi
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, England2Department of Ophthalmology, King's College London, London, England.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
mesh_terms: D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000473:pathology; D015331:Cohort Studies; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012030:Refractive Errors / Q000175:diagnosis* / Q000235:genetics*; D009435:Synaptic Transmission; D018433:Twin Studies as Topic; D006113:United Kingdom
chemical_list: D002118:Calcium