6533b832fe1ef96bd129a344
RESEARCH PRODUCT
Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium
Paul MitchellPaul MitchellArne SchillertTanja ZellerBeate St PourcainYi LuChristopher J HammondNicholas G. MartinRené HöhnVeluchamy A BarathiTerri L. YoungTerri L. YoungJohannes R. VingerlingMario PirastuVeronique VitartAndré G. UitterlindenVirginie J. M. VerhoevenFederico MurgiaXin ZhouPirro G. HysiChristian GiegerJeremy A. GuggenheimRobert WojciechowskiRobert WojciechowskiPaul G. SanfilippoAlireza MirshahiCaroline HaywardTerho LehtimäkiPhillippa M. CumberlandCaroline C W KlaverKonrad OexleTin AungAlan F. WrightEranga N. VithanaPaul N. BairdQiao FanChing-yu ChengAndrew D. PatersonJoan E. Bailey-wilsonThomas MeitingerM. Kamran IkramJanina S. RiedYouchan ShinAlbert HofmanDavid A. MackeyDavid A. MackeyLennart C. KarssenJames F. WilsonGeorge McmahonNajaf AminBen A. OostraBrian W FleckTien Yin WongOlavi PärssinenCathy WilliamsKari-matti MäkeläKumari NeelamRosalynn SiantarYik Ying TeoAlex W. HewittAlex W. HewittHoi Suen WongOlli T. RaitakariOlli T. RaitakariSeyhan YazarBarbara E.k. KleinJanice LamShea Ping YipEkaterina Yonova-doingChiea Chuen KhorChiea Chuen KhorMaurice YapDavid M. EvansDavid M. EvansHarry CampbellGoran BenčićJost B. JonasJost B. JonasYingfeng ZhengCristina VenturiniCristina VenturiniClaire L. SimpsonS. Mohsen HosseiniDwight StambolianE. Shyong TaiFernando RivadeneiraJuho WedenojaJuho WedenojaJohn P. KempStuart MacgregorQing LiCornelia M. Van DuijnOzren PolasekMika KähönenYa Xing WangKate NorthstoneJugnoo S RahiJugnoo S RahiSeang-mei SawKarl J. LacknerNicholas J. Timpsonsubject
MaleRefractive errorBLUE MOUNTAINS EYECORNEAL ASTIGMATISMSpherical equivalentGenome-wide association studyastigmatism; gene; SNPDISEASECohort Studies0302 clinical medicineStatisticsGenetics(clinical)Neural Cell Adhesion MoleculesPOPULATIONGenetics (clinical)Original InvestigationGenetics0303 health scienceseducation.field_of_studyAge FactorsHigh Mobility Group ProteinsMiddle Aged3142 Public health care science environmental and occupational health3. Good healthFemaleOPEN-ANGLE GLAUCOMAAdultGenetic MarkersEXPERIMENTALLY-INDUCED MYOPIAKeratoconusSUSCEPTIBILITY LOCICell Adhesion Molecules NeuronaleducationPopulationNerve Tissue ProteinsAstigmatismBiologyWhite People03 medical and health sciencesAGEAsian PeopleMAJOR LOCUSmedicineGeneticsHumans3125 Otorhinolaryngology ophthalmologyeducation030304 developmental biologyGenetic associationCalcium-Binding ProteinsAstigmatismHeritabilitymedicine.diseaseNONCODING RNAS030221 ophthalmology & optometryGenome-Wide Association Studydescription
To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors. Electronic supplementary material The online version of this article (doi:10.1007/s00439-014-1500-y) contains supplementary material, which is available to authorized users.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-02-01 |