Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Autor: Yonova-Doing E; Department of Twin Research and Genetic Epidemiology, The School of Life Course Sciences, King's College London, London, SE1 7EH, UK., Zhao W; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Center for Quantitative Medicine, Duke-NUS Medical School, 169857, Singapore, Singapore., Igo RP Jr; Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 44106, USA., Wang C; Computational and Systems Biology, Genome Institute of Singapore, 138672, Singapore, Singapore.; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China., Sundaresan P; Department of Genetics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, 625020, India., Lee KE; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA., Jun GR; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, 02118, USA., Alves AC; Department of Twin Research and Genetic Epidemiology, The School of Life Course Sciences, King's College London, London, SE1 7EH, UK., Chai X; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Chan ASY; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore.; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, 169857, Singapore, Singapore., Lee MC; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore., Fong A; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Tan AG; Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia., Khor CC; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Division of Human Genetics, Genome Institute of Singapore, 138672, Singapore, Singapore., Chew EY; National Eye Institute, National Institutes of Health, Bethesda, MD, 20814, USA., Hysi PG; Department of Twin Research and Genetic Epidemiology, The School of Life Course Sciences, King's College London, London, SE1 7EH, UK.; Department of Ophthalmology, King's College London, London, SE5 9RS, UK., Fan Q; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Center for Quantitative Medicine, Duke-NUS Medical School, 169857, Singapore, Singapore., Chua J; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore., Chung J; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore., Liao J; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Colijn JM; Department of Epidemiology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands.; Department of Ophthalmology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands., Burdon KP; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.; Department of Ophthalmology, Flinders University, 5042, Adelaide, SA, Australia., Fritsche LG; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, 7491, Trondheim, Norway., Swift MK; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA., Hilmy MH; Department of Anatomical Pathology and Cytology, Singapore General Hospital, 169608, Singapore, Singapore., Chee ML; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Tedja M; Department of Epidemiology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands.; Department of Ophthalmology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands., Bonnemaijer PWM; Department of Epidemiology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands.; Department of Ophthalmology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands., Gupta P; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Tan QS; Institute of Molecular and Cell Biology, 138673, Singapore, Singapore., Li Z; Division of Human Genetics, Genome Institute of Singapore, 138672, Singapore, Singapore., Vithana EN; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore., Ravindran RD; Aravind Eye Hospital, Madurai, Tamil Nadu, 625020, India., Chee SP; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore., Shi Y; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Liu W; Division of Human Genetics, Genome Institute of Singapore, 138672, Singapore, Singapore., Su X; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Institute of Molecular and Cell Biology, 138673, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore., Sim X; Saw Swee Hock School of Public Health, National University of Singapore, 117549, Singapore, Singapore., Shen Y; Computational and Systems Biology, Genome Institute of Singapore, 138672, Singapore, Singapore., Wang YX; Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, WC29+WV, Beijing, China., Li H; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Tham YC; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore., Teo YY; Saw Swee Hock School of Public Health, National University of Singapore, 117549, Singapore, Singapore.; Department of Statistics and Applied Probability, National University of Singapore, 119077, Singapore, Singapore., Aung T; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore., Small KS; Department of Twin Research and Genetic Epidemiology, The School of Life Course Sciences, King's College London, London, SE1 7EH, UK., Mitchell P; Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia., Jonas JB; Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, WC29+WV, Beijing, China.; Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Seegartenklinik Heidelberg, 69115, Heidelberg, Germany., Wong TY; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore., Fletcher AE; Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Seegartenklinik Heidelberg, 69115, Heidelberg, Germany.; Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Klaver CCW; Department of Epidemiology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands.; Department of Ophthalmology, Erasmus Medical Centre, 3015 GD, Rotterdam, The Netherlands.; Department Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.; Institute of Molecular and Clinical Ophthalmology, Basel, Basel, Switzerland., Klein BEK; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA., Wang JJ; Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia.; Health Services and Systems Research, Duke-NUS Medical School, 169857, Singapore, Singapore., Iyengar SK; Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 44106, USA., Hammond CJ; Department of Twin Research and Genetic Epidemiology, The School of Life Course Sciences, King's College London, London, SE1 7EH, UK. chris.hammond@kcl.ac.uk.; Department of Ophthalmology, King's College London, London, SE5 9RS, UK. chris.hammond@kcl.ac.uk., Cheng CY; Singapore Eye Research Institute, Singapore National Eye Center, 168751, Singapore, Singapore. chingyu.cheng@duke-nus.edu.sg.; Histology, Department of Pathology, Singapore General Hospital, 169856, Singapore, Singapore. chingyu.cheng@duke-nus.edu.sg.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore. chingyu.cheng@duke-nus.edu.sg.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Dec 11; Vol. 3 (1), pp. 755. Date of Electronic Publication: 2020 Dec 11.
DOI: 10.1038/s42003-020-01421-2
Abstrakt: Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h 2  = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10 -16 ) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10 -19 ), TMPRSS5 (rs4936279, P = 2.5 × 10 -10 ), LINC01412 (rs16823886, P = 1.3 × 10 -9 ), GLTSCR1 (rs1005911, P = 9.8 × 10 -9 ), and COMMD1 (rs62149908, P = 1.2 × 10 -8 ). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.
Databáze: MEDLINE
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