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RESEARCH PRODUCT
Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.
Chee Wai WongYoshikatsu HosodaAnnette KifleyYee Ling WongYee Ling WongSusanne HopfAnnechien E. G. HaarmanPaul MitchellTien Yin WongGemmy CheungVirginie J. M. VerhoevenKyoko Ohno-matsuiMoritz HessMoritz HessTerri L. YoungAkitaka TsujikawaKristina N. WhisenhuntSeang-mei SawSonoko SensakiPirro G. HysiPanagiotis LaspasStefan NickelsKenji YamashiroMasahiro MiyakeVeluchamy A BarathiQuan V HoangQuan V HoangJie Jin WangWanting ZhaoChristopher J HammondEcosse L. LamoureuxChing-yu ChengStuart W. TompsonCaroline C W KlaverCaroline C W KlaverMilly S. TedjaXueling Simsubject
Refractive errorCandidate genegenetic structuresEmmetropiaGenome-wide association studySensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Macular DegenerationMathematical and Statistical TechniquesMedicine and Health SciencesMyopiaGeriatric OphthalmologyDioptreVisual ImpairmentsAged 80 and overMultidisciplinaryQRetinal DegenerationStatisticsRGenomicsMetaanalysisPhenotypeResearch DesignPhysical SciencesMedicineRetinal DisordersFemaleAnatomyResearch Articlemedicine.medical_specialtyScienceOcular AnatomySingle-nucleotide polymorphismResearch and Analysis MethodsRetinaOcular SystemOphthalmologyGeneticsGenome-Wide Association StudiesmedicineHumansStatistical Methodsbusiness.industryGene Expression ProfilingCase-control studyBiology and Life SciencesComputational BiologyGenetic VariationCorrectionHuman GeneticsMacular degenerationGenome Analysismedicine.diseaseeye diseasesOphthalmologyGenetic LociGeriatricsMacular DisordersCase-Control StudiesEyessense organsbusinessHeadMathematicsdescription
Purpose: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). Methods: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16, 275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). Results: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16, 275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. Conclusions: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-08-15 | PloS one |