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1. Rare variant analyses across multiethnic cohorts identify novel genes for refractive error.

Author: Musolf, A.M., Haarman, A.E.G., Luben, R.N., Ong, J.S., Patasova, K., Trapero, R.H., Marsh, J., Jain, I., Jain, R., Wang, P.Z., Lewis, D.D., Tedja, M.S., Iglesias, A.I., Li, Hengtong, Cowan, C.S., Biino, G., Klein, A.P., Duggal, P., Mackey, D.A., Hayward, C., Haller, T., Metspalu, A., Wedenoja, J., Pärssinen, O., Cheng, C.Y., Saw, S.M., Stambolian, D., Hysi, P.G., Khawaja, A.P., Vitart, V., Hammond, C.J., Duijn, C.M. van, Verhoeven, V.J.M., Klaver, C.C.W., Bailey-Wilson, J.E., Musolf, A.M., Haarman, A.E.G., Luben, R.N., Ong, J.S., Patasova, K., Trapero, R.H., Marsh, J., Jain, I., Jain, R., Wang, P.Z., Lewis, D.D., Tedja, M.S., Iglesias, A.I., Li, Hengtong, Cowan, C.S., Biino, G., Klein, A.P., Duggal, P., Mackey, D.A., Hayward, C., Haller, T., Metspalu, A., Wedenoja, J., Pärssinen, O., Cheng, C.Y., Saw, S.M., Stambolian, D., Hysi, P.G., Khawaja, A.P., Vitart, V., Hammond, C.J., Duijn, C.M. van, Verhoeven, V.J.M., Klaver, C.C.W., and Bailey-Wilson, J.E.
Abstract: Item does not contain fulltext, Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.
Published: 2023

2. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study

Author: Bourne R. R. A., Steinmetz J. D., Saylan M., Mersha A. M., Weldemariam A. H., Wondmeneh T. G., Sreeramareddy C. T., Pinheiro M., Yaseri M., Yu C., Zastrozhin M. S., Zastrozhina A., Zhang Z. -J., Zimsen S. R. M., Yonemoto N., Tsegaye G. W., Vu G. T., Vongpradith A., Renzaho A. M. N., Sorrie M. B., Shaheen A. A., Shiferaw W. S., Skryabin V. Y., Skryabina A. A., Saya G. K., Rahimi-Movaghar V., Shigematsu M., Sahraian M. A., Naderifar H., Sabour S., Rathi P., Sathian B., Miller T. R., Rezapour A., Rawal L., Pham H. Q., Parekh U., Podder V., Onwujekwe O. E., Pasovic M., Otstavnov N., Negash H., Pawar S., Naimzada M. D., Al Montasir A., Ogbo F. A., Owolabi M. O., Pakshir K., Mohammad Y., Moni M. A., Nunez-Samudio V., Mulaw G. F., Naveed M., Maleki S., Michalek I. M., Misra S., Swamy S. N., Mohammed J. A., Flaxman S., Park E. -C., Briant P. S., Meles G. G., Hayat K., Landires I., Kim G. R., Liu X., LeGrand K. E., Taylor H. R., Kunjathur S. M., Khoja T. A. M., Bicer B. K., Khalilov R., Hashi A., Kayode G. A., Carneiro V. L. A., Kavetskyy T., Kosen S., Kulkarni V., Holla R., Kalhor R., Jayaram S., Islam S. M. S., Gilani S. A., Eskandarieh S., Molla M. D., Itumalla R., Farzadfar F., Congdon N. G., Elhabashy H. R., Elayedath R., Couto R. A. S., Dervenis N., Cromwell E. A., Dahlawi S. M. A., Resnikoff S., Casson R. J., Abdoli A., Choi J. -Y. J., Dos Santos F. L. C., Abrha W. A., Nagaraja S. B., Abualhasan A., Adal T. G., Aregawi B. B., Beheshti M., Abu-Gharbieh E., Afshin A., Ahmadieh H., Alemzadeh S. A., Arrigo A., Atnafu D. D., Ashbaugh C., Ashrafi E., Alemayehu W., Alfaar A. S., Alipour V., Anbesu E. W., Androudi S., Arabloo J., Arditi A., Bagli E., Baig A. A., Barnighausen T. W., Battaglia Parodi M., Bhagavathula A. S., Bhardwaj N., Bhardwaj P., Bhattacharyya K., Bijani A., Bikbov M., Bottone M., Braithwaite T., Bron A. M., Butt Z. A., Cheng C. -Y., Chu D. -T., Cicinelli M. V., Coelho J. M., Dai X., Dana R., Dandona L., Dandona R., Del Monte M. A., Deva J. P., Diaz D., Djalalinia S., Dreer L. E., Ehrlich J. R., Ellwein L. B., Emamian M. H., Fernandes A. G., Fischer F., Friedman D. S., Furtado J. M., Gaidhane S., Gazzard G., Gebremichael B., George R., Ghashghaee A., Golechha M., Hamidi S., Hammond B. R., Hartnett M. E. R., Hartono R. K., Hay S. I., Heidari G., Ho H. C., Househ M., Ibitoye S. E., Ilic I. M., Huang J. J., Ilic M. D., Ingram A. D., Irvani S. S. N., Jha R. P., Kahloun R., Kandel H., Kasa A. S., Kempen J. H., Khairallah M., Khan E. A., Khanna R. C., Khatib M. N., Kim J. E., Kim Y. J., Kisa A., Kisa S., Koyanagi A., Kurmi O. P., Lansingh V. C., Leasher J. L., Leveziel N., Limburg H., Manafi N., Mansouri K., McAlinden C., Mohammadi S. F., Mokdad A. H., Morse A. R., Naderi M., Naidoo K. S., Nangia V., Nguyen H. L. T., Ogundimu K., Olagunju A. T., Panda-Jonas S., Pesudovs K., Peto T., Ur Rahman M. H., Ramulu P. Y., Rawaf D. L., Rawaf S., Reinig N., Robin A. L., Rossetti L., Safi S., Sahebkar A., Samy A. M., Serle J. B., Shaikh M. A., Shen T. T., Shibuya K., Shin J. I., Silva J. C., Silvester A., Singh J. A., Singhal D., Sitorus R. S., Skiadaresi E., Soheili A., Sousa R. A. R. C., Stambolian D., Tadesse E. G., Tahhan N., Tareque Md. I., Topouzis F., Tran B. X., Tsilimbaris M. K., Varma R., Virgili G., Wang N., Wang Y. X., West S. K., Wong T. Y., Jonas J. B., Vos T., Bourne, R. R. A., Steinmetz, J. D., Saylan, M., Mersha, A. M., Weldemariam, A. H., Wondmeneh, T. G., Sreeramareddy, C. T., Pinheiro, M., Yaseri, M., Yu, C., Zastrozhin, M. S., Zastrozhina, A., Zhang, Z. -J., Zimsen, S. R. M., Yonemoto, N., Tsegaye, G. W., Vu, G. T., Vongpradith, A., Renzaho, A. M. N., Sorrie, M. B., Shaheen, A. A., Shiferaw, W. S., Skryabin, V. Y., Skryabina, A. A., Saya, G. K., Rahimi-Movaghar, V., Shigematsu, M., Sahraian, M. A., Naderifar, H., Sabour, S., Rathi, P., Sathian, B., Miller, T. R., Rezapour, A., Rawal, L., Pham, H. Q., Parekh, U., Podder, V., Onwujekwe, O. E., Pasovic, M., Otstavnov, N., Negash, H., Pawar, S., Naimzada, M. D., Al Montasir, A., Ogbo, F. A., Owolabi, M. O., Pakshir, K., Mohammad, Y., Moni, M. A., Nunez-Samudio, V., Mulaw, G. F., Naveed, M., Maleki, S., Michalek, I. M., Misra, S., Swamy, S. N., Mohammed, J. A., Flaxman, S., Park, E. -C., Briant, P. S., Meles, G. G., Hayat, K., Landires, I., Kim, G. R., Liu, X., Legrand, K. E., Taylor, H. R., Kunjathur, S. M., Khoja, T. A. M., Bicer, B. K., Khalilov, R., Hashi, A., Kayode, G. A., Carneiro, V. L. A., Kavetskyy, T., Kosen, S., Kulkarni, V., Holla, R., Kalhor, R., Jayaram, S., Islam, S. M. S., Gilani, S. A., Eskandarieh, S., Molla, M. D., Itumalla, R., Farzadfar, F., Congdon, N. G., Elhabashy, H. R., Elayedath, R., Couto, R. A. S., Dervenis, N., Cromwell, E. A., Dahlawi, S. M. A., Resnikoff, S., Casson, R. J., Abdoli, A., Choi, J. -Y. J., Dos Santos, F. L. C., Abrha, W. A., Nagaraja, S. B., Abualhasan, A., Adal, T. G., Aregawi, B. B., Beheshti, M., Abu-Gharbieh, E., Afshin, A., Ahmadieh, H., Alemzadeh, S. A., Arrigo, A., Atnafu, D. D., Ashbaugh, C., Ashrafi, E., Alemayehu, W., Alfaar, A. S., Alipour, V., Anbesu, E. W., Androudi, S., Arabloo, J., Arditi, A., Bagli, E., Baig, A. A., Barnighausen, T. W., Battaglia Parodi, M., Bhagavathula, A. S., Bhardwaj, N., Bhardwaj, P., Bhattacharyya, K., Bijani, A., Bikbov, M., Bottone, M., Braithwaite, T., Bron, A. M., Butt, Z. A., Cheng, C. -Y., Chu, D. -T., Cicinelli, M. V., Coelho, J. M., Dai, X., Dana, R., Dandona, L., Dandona, R., Del Monte, M. A., Deva, J. P., Diaz, D., Djalalinia, S., Dreer, L. E., Ehrlich, J. R., Ellwein, L. B., Emamian, M. H., Fernandes, A. G., Fischer, F., Friedman, D. S., Furtado, J. M., Gaidhane, S., Gazzard, G., Gebremichael, B., George, R., Ghashghaee, A., Golechha, M., Hamidi, S., Hammond, B. R., Hartnett, M. E. R., Hartono, R. K., Hay, S. I., Heidari, G., Ho, H. C., Househ, M., Ibitoye, S. E., Ilic, I. M., Huang, J. J., Ilic, M. D., Ingram, A. D., Irvani, S. S. N., Jha, R. P., Kahloun, R., Kandel, H., Kasa, A. S., Kempen, J. H., Khairallah, M., Khan, E. A., Khanna, R. C., Khatib, M. N., Kim, J. E., Kim, Y. J., Kisa, A., Kisa, S., Koyanagi, A., Kurmi, O. P., Lansingh, V. C., Leasher, J. L., Leveziel, N., Limburg, H., Manafi, N., Mansouri, K., Mcalinden, C., Mohammadi, S. F., Mokdad, A. H., Morse, A. R., Naderi, M., Naidoo, K. S., Nangia, V., Nguyen, H. L. T., Ogundimu, K., Olagunju, A. T., Panda-Jonas, S., Pesudovs, K., Peto, T., Ur Rahman, M. H., Ramulu, P. Y., Rawaf, D. L., Rawaf, S., Reinig, N., Robin, A. L., Rossetti, L., Safi, S., Sahebkar, A., Samy, A. M., Serle, J. B., Shaikh, M. A., Shen, T. T., Shibuya, K., Shin, J. I., Silva, J. C., Silvester, A., Singh, J. A., Singhal, D., Sitorus, R. S., Skiadaresi, E., Soheili, A., Sousa, R. A. R. C., Stambolian, D., Tadesse, E. G., Tahhan, N., Tareque, Md. I., Topouzis, F., Tran, B. X., Tsilimbaris, M. K., Varma, R., Virgili, G., Wang, N., Wang, Y. X., West, S. K., Wong, T. Y., Jonas, J. B., Vos, T., University of Washington [Seattle], Anglia Ruskin University (ARU), Imperial College London, University of Melbourne, Heidelberg University, Jahrom University of Medical Sciences, Aksum University, Cairo University, University of Sharjah, Wolkite University, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, The Fred Hollows Foundation, Iran University of Medical Sciences, University of Leipzig Medical Center, University of Thessaly [Volos] (UTH), Visibility Metrics LLC, Adigrat University, San Raffaele Hospital, Tehran University of Medical Sciences (TUMS), Bahir Dar University (BDU), University Hospital of Ioannina, Sultan Zainal Abidin University, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Charles University [Prague] (CU), Government Medical College Pali, All India Institute of Medical Sciences, National Institute of Biomedical Genomics, Babol University of Medical Sciences, Ufa Eye Research Institute, ondon School of Hygiene & Tropical Medicine, Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Employee State Insurance Post Graduate Institute of Medical Sciences and Research, University of Waterloo [Waterloo], Federal Polytechnic School of Lausanne, University of Minho, University of Adelaide, Singapore Eye Research Institute [Singapore] (SERI), Seoul National University Hospital, Hanoi National University of Education (HNUE), IRCCS San Raffaele Scientific Institute [Milan, Italie], University of Porto, Queen's University [Belfast] (QUB), University of Dammam - Imam Abdulrahman Bin Faisal University, Harvard University, University of Michigan [Ann Arbor], University of Michigan System, University of Gondar, Royal Liverpool University Hospital, Universiti Tunku Abdul Rahman (UTAR), National Autonomous University of Mexico (UNAM), Ministry of Health and Medical Education [Iran] (MOHME), Mahatma Gandhi University of Medical Sciences and Technology, Cairo University - Faculty of Medicine, National Institutes of Health [Bethesda] (NIH), Shahroud University of Medical Sciences, Federal University of Sao Paulo (Unifesp), University of Applied Sciences Ravensburg-Weingarten, University of São Paulo (USP), Datta Meghe Institute of Medical Sciences, University College of London [London] (UCL), Haramaya University, Sankara Nethralaya Medical Research Foundation, The University of Lahore, Indian Institute of Public Health Gandhinagar, Hamdan Bin Mohammed Smart University, University of Georgia, University of Utah, Institution of Public Health Sciences, Jigjiga Universit, University of Veterinary and Animal Sciences, Independent Consultant, The Chinese University of Hong Kong [Hong Kong], Manipal academy of Higher Education, Hamad Bin Khalifa University (HBKU), Yale University [New Haven], University of Ibadan, University of Belgrade [Belgrade], Faculty of Science of the University of Kragujevac, University of Kragujevac, Deakin University, Burwood, Australia, Deakin University [Burwood], University of Hail, Mysore Medical College, Banaras Hindu University [Varanasi] (BHU), Ophtalmologistes Associe Monastir, Qazvin University of Medical Sciences, The University of Sydney, John Paul II Catholic University of Lublin (KUL), Institute of Human Virology [Nigeria] (IHVN), Myungsung Medical College, Centre Hospitalier Universitaire Fattouma Bourguiba, Partenaires INRAE, Baku State University, Health Services Academy, L V Prasad Eye Institute, Health Ministers Council Gulf Cooperative Council Stat, Medical College of Wisconsin [Milwaukee] (MCW), Xiamen University Malaysia, Yonsei University, Oslo Metropolitan University (OsloMet), School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia, Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg., and GBD 2019 Blindness and Vision Impairment Collaborators* on behalf of the Vision Loss Expert Group of the Global Burden of Disease Study.
Subjects: Pediatrics, medicine.medical_specialty, Refractive error, Visual acuity, genetic structures, Eye disease, 030231 tropical medicine, Population, Glaucoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Global health, 030212 general & internal medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, education.field_of_study, business.industry, Articles, General Medicine, Diabetic retinopathy, Macular degeneration, medicine.disease, eye diseases, 3. Good health, medicine.symptom, business
Abstract: Background: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from
Published: 2021

3. Prevalence and causes of vision loss in sub-Saharan Africa in 2015: magnitude, temporal trends and projections

Author: Naidoo, Kovin, Kempen, John H, Gichuhi, Stephen, Braithwaite, Tasanee, Casson, Robert J, Cicinelli, Maria Vittoria, Das, Aditi, Flaxman, Seth R, Jonas, Jost B, Keeffe, Jill Elizabeth, Leasher, Janet, Limburg, Hans, Pesudovs, Konrad, Resnikoff, Serge, Silvester, Alexander J, Tahhan, Nina, Taylor, Hugh R, Wong, Tien Y, Bourne, Rupert R A, Vision Loss Expert Group of the Global Burden of Disease Study. Collaborators (Bourne R, Ackland P, Arditi A, Barkana Y, Bozkurt B, Tasanee B, Bron A, Budenz D, Cai F, Casson R, Chakravarthy U, Choi J, Cicinelli MV, Congdon N, Dana R, Dandona R, Dandona L, Das A, Dekaris I, Monte Del Monte MD, Deva J, Dirani M, Dreer L, Ellwein L, Frazier M, Frick K, Friedman D, Furtado J, Gao H, Gazzard A, George R, Gichuhi S, Gonzalez V, Hammond B, Hartnett ME, He M, Hejtmancik J, Hirai F, Huang J, Ingram A, Javitt J, Jonas J, Joslin C, Keeffe J, Kempen J, Khairallah M, Khanna R, Kim J, Lambrou G, Lansingh VC, Lanzetta P, Leasher J, Lim J, Hans L, Mansouri K, Mathew A, Morse A, Munoz B, Musch D, Naidoo K, Nangia V, Maria P, Battaglia Parodi M, Pena FY, Pesudovs K, Peto T, Quigley H, Raju M, Ramulu P, Resnikoff S, Reza D, Robin A, Rossetti L, Saaddine J, Sandar M, Serle J, Shen T, Shetty R, Sieving P, Silva JC, Silvester A, Sitorus RS, Stambolian D, Stevens G, Taylor H, Tejedor J, Tielsch J, Topouzis F, Tsilimbaris M, Meurs JV, Varma R, Virgili G, Volmink J, Wang YX, Ning-Li Wang SW, Wiedemann P, Wong T, Wormald R, Zheng Y, Flaxman S)., Naidoo, Kovin, Kempen, John H, Gichuhi, Stephen, Braithwaite, Tasanee, Casson, Robert J, Cicinelli, Maria Vittoria, Das, Aditi, Flaxman, Seth R, Jonas, Jost B, Keeffe, Jill Elizabeth, Leasher, Janet, Limburg, Han, Pesudovs, Konrad, Resnikoff, Serge, Silvester, Alexander J, Tahhan, Nina, Taylor, Hugh R, Wong, Tien Y, Bourne, Rupert R A, Vision Loss Expert Group of the Global Burden of Disease Study., Collaborators (Bourne R, Ackland, P, Arditi, A, Barkana, Y, Bozkurt, B, Tasanee, B, Bron, A, Budenz, D, Cai, F, Casson, R, Chakravarthy, U, Choi, J, Cicinelli, Mv, Congdon, N, Dana, R, Dandona, R, Dandona, L, Das, A, Dekaris, I, Monte Del Monte, Md, Deva, J, Dirani, M, Dreer, L, Ellwein, L, Frazier, M, Frick, K, Friedman, D, Furtado, J, Gao, H, Gazzard, A, George, R, Gichuhi, S, Gonzalez, V, Hammond, B, Hartnett, Me, He, M, Hejtmancik, J, Hirai, F, Huang, J, Ingram, A, Javitt, J, Jonas, J, Joslin, C, Keeffe, J, Kempen, J, Khairallah, M, Khanna, R, Kim, J, Lambrou, G, Lansingh, Vc, Lanzetta, P, Leasher, J, Lim, J, Hans, L, Mansouri, K, Mathew, A, Morse, A, Munoz, B, Musch, D, Naidoo, K, Nangia, V, Maria, P, Battaglia Parodi, M, Pena, Fy, Pesudovs, K, Peto, T, Quigley, H, Raju, M, Ramulu, P, Resnikoff, S, Reza, D, Robin, A, Rossetti, L, Saaddine, J, Sandar, M, Serle, J, Shen, T, Shetty, R, Sieving, P, Silva, Jc, Silvester, A, Sitorus, R, Stambolian, D, Stevens, G, Taylor, H, Tejedor, J, Tielsch, J, Topouzis, F, Tsilimbaris, M, Meurs, Jv, Varma, R, Virgili, G, Volmink, J, Wang, Yx, Ning-Li Wang, Sw, Wiedemann, P, Wong, T, Wormald, R, Zheng, Y, and Flaxman, S).
Subjects: Refractive error, medicine.medical_specialty, Sub saharan, Visual acuity, Visual Acuity, Glaucoma, Blindness, Cataract, Macular Degeneration, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Epidemiology, Prevalence, Humans, Medicine, 030212 general & internal medicine, Africa South of the Sahara, business.industry, public health, Presbyopia, Macular degeneration, Refractive Errors, medicine.disease, Sensory Systems, Ophthalmology, 030221 ophthalmology & optometry, epidemiology, medicine.symptom, business, Visually Impaired Persons, Forecasting, Demography
Abstract: BackgroundThis study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020.MethodsA systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity In SSA, age-standardised prevalence of blindness, MSVI and MVI in 2015 were 1.03% (80% uncertainty interval (UI) 0.39–1.81), 3.64% (80% UI 1.71–5.94) and 2.94% (80% UI 1.05–5.34), respectively, for male and 1.08% (80% UI 0.40–1.93), 3.84% (80% UI 1.72–6.37) and 3.06% (80% UI 1.07–5.61) for females, constituting a significant decrease since 2010 for both genders. There were an estimated 4.28 million blind individuals and 17.36 million individuals with MSVI; 101.08 million individuals were estimated to have near vision loss due to presbyopia. Cataract was the most common cause of blindness (40.1%), whereas undercorrected refractive error (URE) (48.5%) was the most common cause of MSVI. Sub-Saharan West Africa had the highest proportion of blindness compared with the other SSA subregions.ConclusionsCataract and URE, two of the major causes of blindness and vision impairment, are reversible with treatment and thus promising targets to alleviate vision impairment in SSA.
Published: 2020

4. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study

Author: Steinmetz, JD, Bourne, RRA, Briant, PS, Flaxman, S, Taylor, HR, Jonas, JB, Abdoli, A, Abrha, WA, Abualhasan, A, Abu-Gharbieh, E, Adal, TG, Afshin, A, Ahmadieh, H, Alemayehu, W, Alemzadeh, SA, Alfaar, AS, Alipour, V, Androudi, S, Arabloo, J, Arditi, A, Aregawi, BB, Arrigo, A, Ashbaugh, C, Ashrafi, E, Atnafu, DD, Bagli, E, Baig, AA, Barnighausen, TW, Parodi, MB, Beheshti, M, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, M, Bottone, M, Braithwaite, T, Bron, AM, Nagaraja, SB, Butt, ZA, dos Santos, FLC, Carneiro, VLA, Casson, RJ, Cheng, C-Y, Choi, J-YJ, Chu, D-T, Cicinelli, MV, Coelho, JM, Congdon, NG, Couto, RAS, Cromwell, EA, Dahlawi, SMA, Dai, X, Dana, R, Dandona, L, Dandona, R, Del Monte, MA, Molla, MD, Dervenis, N, Desta, AA, Deva, JP, Diaz, D, Djalalinia, S, Ehrlich, JR, Elayedath, R, Elhabashy, HR, Ellwein, LB, Emamian, MH, Eskandarieh, S, Farzadfar, F, Fernandes, AG, Fischer, F, Friedman, DS, Furtado, JM, Gaidhane, S, Gazzard, G, Gebremichael, B, George, R, Ghashghaee, A, Gilani, SA, Golechha, M, Hamidi, S, Hammond, BR, Hartnett, MER, Hartono, RK, Hashi, A, Hay, S, Hayat, K, Heidari, G, Ho, HC, Holla, R, Househ, M, Huang, JJ, Ibitoye, SE, Ilic, IM, Ilic, MD, Ingram, AD, Irvani, SSN, Islam, SMS, Itumalla, R, Jayaram, S, Jha, RP, Kahloun, R, Kalhor, R, Kandel, H, Kasa, AS, Kavetskyy, T, Kayode, GA, Kempen, JH, Khairallah, M, Khalilov, R, Khan, EA, Khanna, RC, Khatib, MN, Khoja, TAM, Kim, GR, Kim, JE, Kim, YJ, Kisa, A, Kisa, S, Kosen, S, Koyanagi, A, Bicer, BK, Kulkarni, V, Kurmi, OP, Landires, I, Lansingh, VC, Leasher, JL, LeGrand, KE, Leveziel, N, Limburg, H, Liu, X, Kunjathur, SM, Maleki, S, Manafi, N, Mansouri, K, McAlinden, C, Meles, GG, Mersha, AM, Michalek, IM, Miller, TR, Misra, S, Mohammad, Y, Mohammadi, SF, Mohammed, JA, Mokdad, AH, Moni, MA, Al Montasir, A, Morse, AR, Mulaw, GF, Naderi, M, Naderifar, H, Naidoo, KS, Naimzada, MD, Nangia, V, Swamy, SN, Naveed, M, Negash, H, Huong, LTN, Nunez-Samudio, V, Ogbo, FA, Ogundimu, K, Olagunju, AT, Onwujekwe, OE, Otstavnov, N, Owolabi, MO, Pakshir, K, Panda-Jonas, S, Parekh, U, Park, E-C, Pasovic, M, Pawar, S, Pesudovs, K, Peto, T, Pham, HQ, Pinheiro, M, Podder, V, Rahimi-Movaghar, V, Rahman, MHU, Ramulu, PY, Rathi, P, Rawaf, DL, Rawaf, S, Rawal, L, Reinig, N, Renzaho, AMN, Rezapour, A, Robin, AL, Rossetti, L, Sabour, S, Safi, S, Sahebkar, A, Sahraian, MA, Samy, AM, Sathian, B, Saya, GK, Saylan, M, Shaheen, AA, Shaikh, MA, Shen, TT, Shibuya, K, Shiferaw, WS, Shigematsu, M, Shin, JI, Silva, JC, Silvester, A, Singh, JA, Singhal, D, Sitorus, RS, Skiadaresi, E, Skryabin, VY, Skryabina, AA, Soheili, A, Sorrie, MB, Sousa, RARC, Sreeramareddy, CT, Stambolian, D, Tadesse, EG, Tahhan, N, Tareque, MI, Topouzis, F, Bach, XT, Tsegaye, GW, Tsilimbaris, MK, Varma, R, Virgili, G, Vongpradith, A, Vu, GT, Wang, YX, Wang, N, Weldemariam, AH, West, SK, Wondmeneh, TG, Wong, TY, Yaseri, M, Yonemoto, N, Yu, C, Zastrozhin, MS, Zastrozhina, A, Zhang, Z-J, Zimsen, SRM, Resnikoff, S, Vos, T, Steinmetz, JD, Bourne, RRA, Briant, PS, Flaxman, S, Taylor, HR, Jonas, JB, Abdoli, A, Abrha, WA, Abualhasan, A, Abu-Gharbieh, E, Adal, TG, Afshin, A, Ahmadieh, H, Alemayehu, W, Alemzadeh, SA, Alfaar, AS, Alipour, V, Androudi, S, Arabloo, J, Arditi, A, Aregawi, BB, Arrigo, A, Ashbaugh, C, Ashrafi, E, Atnafu, DD, Bagli, E, Baig, AA, Barnighausen, TW, Parodi, MB, Beheshti, M, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, M, Bottone, M, Braithwaite, T, Bron, AM, Nagaraja, SB, Butt, ZA, dos Santos, FLC, Carneiro, VLA, Casson, RJ, Cheng, C-Y, Choi, J-YJ, Chu, D-T, Cicinelli, MV, Coelho, JM, Congdon, NG, Couto, RAS, Cromwell, EA, Dahlawi, SMA, Dai, X, Dana, R, Dandona, L, Dandona, R, Del Monte, MA, Molla, MD, Dervenis, N, Desta, AA, Deva, JP, Diaz, D, Djalalinia, S, Ehrlich, JR, Elayedath, R, Elhabashy, HR, Ellwein, LB, Emamian, MH, Eskandarieh, S, Farzadfar, F, Fernandes, AG, Fischer, F, Friedman, DS, Furtado, JM, Gaidhane, S, Gazzard, G, Gebremichael, B, George, R, Ghashghaee, A, Gilani, SA, Golechha, M, Hamidi, S, Hammond, BR, Hartnett, MER, Hartono, RK, Hashi, A, Hay, S, Hayat, K, Heidari, G, Ho, HC, Holla, R, Househ, M, Huang, JJ, Ibitoye, SE, Ilic, IM, Ilic, MD, Ingram, AD, Irvani, SSN, Islam, SMS, Itumalla, R, Jayaram, S, Jha, RP, Kahloun, R, Kalhor, R, Kandel, H, Kasa, AS, Kavetskyy, T, Kayode, GA, Kempen, JH, Khairallah, M, Khalilov, R, Khan, EA, Khanna, RC, Khatib, MN, Khoja, TAM, Kim, GR, Kim, JE, Kim, YJ, Kisa, A, Kisa, S, Kosen, S, Koyanagi, A, Bicer, BK, Kulkarni, V, Kurmi, OP, Landires, I, Lansingh, VC, Leasher, JL, LeGrand, KE, Leveziel, N, Limburg, H, Liu, X, Kunjathur, SM, Maleki, S, Manafi, N, Mansouri, K, McAlinden, C, Meles, GG, Mersha, AM, Michalek, IM, Miller, TR, Misra, S, Mohammad, Y, Mohammadi, SF, Mohammed, JA, Mokdad, AH, Moni, MA, Al Montasir, A, Morse, AR, Mulaw, GF, Naderi, M, Naderifar, H, Naidoo, KS, Naimzada, MD, Nangia, V, Swamy, SN, Naveed, M, Negash, H, Huong, LTN, Nunez-Samudio, V, Ogbo, FA, Ogundimu, K, Olagunju, AT, Onwujekwe, OE, Otstavnov, N, Owolabi, MO, Pakshir, K, Panda-Jonas, S, Parekh, U, Park, E-C, Pasovic, M, Pawar, S, Pesudovs, K, Peto, T, Pham, HQ, Pinheiro, M, Podder, V, Rahimi-Movaghar, V, Rahman, MHU, Ramulu, PY, Rathi, P, Rawaf, DL, Rawaf, S, Rawal, L, Reinig, N, Renzaho, AMN, Rezapour, A, Robin, AL, Rossetti, L, Sabour, S, Safi, S, Sahebkar, A, Sahraian, MA, Samy, AM, Sathian, B, Saya, GK, Saylan, M, Shaheen, AA, Shaikh, MA, Shen, TT, Shibuya, K, Shiferaw, WS, Shigematsu, M, Shin, JI, Silva, JC, Silvester, A, Singh, JA, Singhal, D, Sitorus, RS, Skiadaresi, E, Skryabin, VY, Skryabina, AA, Soheili, A, Sorrie, MB, Sousa, RARC, Sreeramareddy, CT, Stambolian, D, Tadesse, EG, Tahhan, N, Tareque, MI, Topouzis, F, Bach, XT, Tsegaye, GW, Tsilimbaris, MK, Varma, R, Virgili, G, Vongpradith, A, Vu, GT, Wang, YX, Wang, N, Weldemariam, AH, West, SK, Wondmeneh, TG, Wong, TY, Yaseri, M, Yonemoto, N, Yu, C, Zastrozhin, MS, Zastrozhina, A, Zhang, Z-J, Zimsen, SRM, Resnikoff, S, and Vos, T
Abstract: BACKGROUND: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. METHODS: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. FINDINGS: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change -0·2% [95% UI -1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by -15·4% [-16·8 to -14·3], while avoidable MSVI showed no change (0·5% [-0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7-18·0]), followed by glaucoma (3·6 million cases [2·8-4·4]), undercorrected refractive error (2·3 million cases [1·8-2·8]), age-related macular degeneration (1·8 million cases [1·3-2·4]), and diabetic retinopathy (0·86 mill
Published: 2021

5. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study

Author: Bourne, RRA, Steinmetz, JD, Flaxman, S, Briant, PS, Taylor, HR, Resnikoff, S, Casson, RJ, Abdoli, A, Abu-Gharbieh, E, Afshin, A, Ahmadieh, H, Akalu, Y, Alamneh, AA, Alemayehu, W, Alfaar, AS, Alipour, V, Anbesu, EW, Androudi, S, Arabloo, J, Arditi, A, Asaad, M, Bagli, E, Baig, AA, Barnighausen, TW, Parodi, MB, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, M, Bottone, M, Braithwaite, T, Bron, AM, Butt, ZA, Cheng, C-Y, Chu, D-T, Cicinelli, MV, Coelho, JM, Dagnew, B, Dai, X, Dana, R, Dandona, L, Dandona, R, Del Monte, MA, Deva, JP, Diaz, D, Djalalinia, S, Dreer, LE, Ehrlich, JR, Ellwein, LB, Emamian, MH, Fernandes, AG, Fischer, F, Friedman, DS, Furtado, JM, Gaidhane, AM, Gaidhane, S, Gazzard, G, Gebremichael, B, George, R, Ghashghaee, A, Golechha, M, Hamidi, S, Hammond, BR, Hartnett, MER, Hartono, RK, Hay, S, Heidari, G, Ho, HC, Chi, LH, Househ, M, Ibitoye, SE, Ilic, IM, Ilic, MD, Ingram, AD, Irvani, SSN, Jha, RP, Kahloun, R, Kandel, H, Kasa, AS, Kempen, JH, Keramati, M, Khairallah, M, Khan, EA, Khanna, RC, Khatib, MN, Kim, JE, Kim, YJ, Kisa, A, Kisa, S, Koyanagi, A, Kurmi, OP, Lansingh, VC, Leasher, JL, Leveziel, N, Limburg, H, Majdan, M, Manafi, N, Mansouri, K, McAlinden, C, Mohammadi, SF, Mohammadian-Hafshejani, A, Mohammadpourhodki, R, Mokdad, AH, Moosavi, D, Morse, AR, Naderi, M, Naidoo, KS, Nangia, V, Cuong, TN, Huong, LTN, Ogundimu, K, Olagunju, AT, Ostroff, SM, Panda-Jonas, S, Pesudovs, K, Peto, T, Syed, ZQ, Rahman, MHU, Ramulu, PY, Rawaf, DL, Rawaf, S, Reinig, N, Robin, AL, Rossetti, L, Safi, S, Sahebkar, A, Samy, AM, Saxena, D, Serle, JB, Shaikh, MA, Shen, TT, Shibuya, K, Shin, JI, Silva, JC, Silvester, A, Singh, JA, Singhal, D, Sitorus, RS, Skiadaresi, E, Skirbekk, V, Soheili, A, Sousa, RARC, Spurlock, EE, Stambolian, D, Taddele, BW, Tadesse, EG, Tahhan, N, Tareque, MI, Topouzis, F, Bach, XT, Travillian, RS, Tsilimbaris, MK, Varma, R, Virgili, G, Wang, N, Wang, YX, West, SK, Wong, TY, Zaidi, Z, Zewdie, KA, Jonas, JB, Vos, T, Bourne, RRA, Steinmetz, JD, Flaxman, S, Briant, PS, Taylor, HR, Resnikoff, S, Casson, RJ, Abdoli, A, Abu-Gharbieh, E, Afshin, A, Ahmadieh, H, Akalu, Y, Alamneh, AA, Alemayehu, W, Alfaar, AS, Alipour, V, Anbesu, EW, Androudi, S, Arabloo, J, Arditi, A, Asaad, M, Bagli, E, Baig, AA, Barnighausen, TW, Parodi, MB, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, M, Bottone, M, Braithwaite, T, Bron, AM, Butt, ZA, Cheng, C-Y, Chu, D-T, Cicinelli, MV, Coelho, JM, Dagnew, B, Dai, X, Dana, R, Dandona, L, Dandona, R, Del Monte, MA, Deva, JP, Diaz, D, Djalalinia, S, Dreer, LE, Ehrlich, JR, Ellwein, LB, Emamian, MH, Fernandes, AG, Fischer, F, Friedman, DS, Furtado, JM, Gaidhane, AM, Gaidhane, S, Gazzard, G, Gebremichael, B, George, R, Ghashghaee, A, Golechha, M, Hamidi, S, Hammond, BR, Hartnett, MER, Hartono, RK, Hay, S, Heidari, G, Ho, HC, Chi, LH, Househ, M, Ibitoye, SE, Ilic, IM, Ilic, MD, Ingram, AD, Irvani, SSN, Jha, RP, Kahloun, R, Kandel, H, Kasa, AS, Kempen, JH, Keramati, M, Khairallah, M, Khan, EA, Khanna, RC, Khatib, MN, Kim, JE, Kim, YJ, Kisa, A, Kisa, S, Koyanagi, A, Kurmi, OP, Lansingh, VC, Leasher, JL, Leveziel, N, Limburg, H, Majdan, M, Manafi, N, Mansouri, K, McAlinden, C, Mohammadi, SF, Mohammadian-Hafshejani, A, Mohammadpourhodki, R, Mokdad, AH, Moosavi, D, Morse, AR, Naderi, M, Naidoo, KS, Nangia, V, Cuong, TN, Huong, LTN, Ogundimu, K, Olagunju, AT, Ostroff, SM, Panda-Jonas, S, Pesudovs, K, Peto, T, Syed, ZQ, Rahman, MHU, Ramulu, PY, Rawaf, DL, Rawaf, S, Reinig, N, Robin, AL, Rossetti, L, Safi, S, Sahebkar, A, Samy, AM, Saxena, D, Serle, JB, Shaikh, MA, Shen, TT, Shibuya, K, Shin, JI, Silva, JC, Silvester, A, Singh, JA, Singhal, D, Sitorus, RS, Skiadaresi, E, Skirbekk, V, Soheili, A, Sousa, RARC, Spurlock, EE, Stambolian, D, Taddele, BW, Tadesse, EG, Tahhan, N, Tareque, MI, Topouzis, F, Bach, XT, Travillian, RS, Tsilimbaris, MK, Varma, R, Virgili, G, Wang, N, Wang, YX, West, SK, Wong, TY, Zaidi, Z, Zewdie, KA, Jonas, JB, and Vos, T
Abstract: BACKGROUND: To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990-2020, and forecasts for 2050. METHODS: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals [UIs]) of mild vision impairment (presenting visual acuity ≥6/18 and <6/12), moderate and severe vision impairment (<6/18 to 3/60), and blindness (<3/60 or less than 10° visual field around central fixation); and vision impairment from uncorrected presbyopia (presenting near vision
Published: 2021

6. Genetic susceptibility and mechanisms for refractive error

Author: Stambolian, D
Published: 2013
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7. Transcriptome analysis and molecular signature of human retinal pigment epithelium

Author: Strunnikova, N.V., Maminishkis, A., Barb, J.J., Wang, F., Zhi, C., Sergeev, Y., Chen, W., Edwards, A.O., Stambolian, D., Abecasis, G., Swaroop, A., Munson, P.J., and Miller, S.S.
Published: 2010
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8. The mouse Cat4 locus maps to Chromosome 8 and mutants express lens-corneal adhesion

Author: Favor, J., Grimes, P., Neuhäuser-Klaus, A., Pretsch, W., and Stambolian, D.
Published: 1997
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9. Genetic mapping of a mouse ocular malformation locus, tcm, to chromosome 4

Author: Zhou, E., Grimes, P., Favor, J., Koeberlein, B., Pretsch, W., Neuhauser-Klaus, A., Sidjanin, D., and Stambolian, D.
Published: 1997
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10. Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

Author: Iglesias González, A.I. (Adriana), Ong, J.S., Khawaja, AP, Gharahkhani, P, Tedja, M.S., Verhoeven, V.J.M. (Virginie), Bonnemaijer, P.W.M. (Pieter), Wolfs, R.C.W. (Roger), Young, T.L. (Terri), Jansonius, NM, Craig, J.E. (Jamie), Stambolian, D, Duijn, C.M., MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), Iglesias González, A.I. (Adriana), Ong, J.S., Khawaja, AP, Gharahkhani, P, Tedja, M.S., Verhoeven, V.J.M. (Virginie), Bonnemaijer, P.W.M. (Pieter), Wolfs, R.C.W. (Roger), Young, T.L. (Terri), Jansonius, NM, Craig, J.E. (Jamie), Stambolian, D, Duijn, C.M., MacGregor, S. (Stuart), and Klaver, C.C.W. (Caroline)
Abstract: PURPOSE. To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS. We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS. We did not find significant evidence for an association between PRS of myopia with POAG (P ¼ 0.81), IOP (P ¼ 0.07), vertical cup–disc ratio (P ¼ 0.42), or cup area (P ¼ 0.25). We observed a nominal association with retinal nerve fiber layer (P ¼ 7.7 3 103 ) and a significant association between PRS for myopia and disc area (P ¼ 1.59 3 109 ). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] ¼ 0.12, P ¼ 1.8 3 103 ), supporting the findings of the PRS approach. CONCLUSIONS. Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.
Published: 2019
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11. Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

Author: Iglesias, AI, Ong, JS, Khawaja, AP, Gharahkhani, P, Tedja, MS, Verhoeven, VJM, Bonnemaijer, PWM, Wolfs, RCW, Young, TL, Jansonius, NM, Craig, JE, Stambolian, D, van Duijn, CM, MacGregor, S, Klaver, CCW, Iglesias, AI, Ong, JS, Khawaja, AP, Gharahkhani, P, Tedja, MS, Verhoeven, VJM, Bonnemaijer, PWM, Wolfs, RCW, Young, TL, Jansonius, NM, Craig, JE, Stambolian, D, van Duijn, CM, MacGregor, S, and Klaver, CCW
Abstract: PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.
Published: 2019

12. IMI - Myopia Genetics Report

Author: Tedja, MS, Haarman, AEG, Meester-Smoor, MA, Kaprio, J, Mackey, DA, Guggenheim, JA, Hammond, CJ, Verhoeven, VJM, Klaver, CCW, Bailey-Wilson, JE, Baird, PN, Veluchamy, AB, Biino, G, Burdon, KP, Campbell, H, Chen, LJ, Cheng, C-Y, Chew, EY, Craig, JE, Cumberland, PM, Deangelis, MM, Delcourt, C, Ding, X, van Duijn, CM, Evans, DM, Fan, Q, Fossarello, M, Foster, PJ, Gharahkhani, P, Iglesias, AI, Guol, X, Haller, T, Han, X, Hayward, C, He, M, Hewitt, AW, Hoang, Q, Hysi, PG, Igo, RP, Iyengar, SK, Jonas, JB, Kahonen, M, Khawaja, AP, Klein, BE, Klein, R, Lass, JH, Lee, K, Lehtimaki, T, Lewis, D, Li, Q, Li, S-M, Lyytikainen, L-P, MacGregor, S, Martin, NG, Meguro, A, Metspalu, A, Middlebrooks, C, Miyake, M, Mizuki, N, Musolf, A, Nickels, S, Oexle, K, Pang, CP, Parssinen, O, Paterson, AD, Pfeiffer, N, Polasek, O, Rahi, JS, Raitakari, O, Rudan, I, Sahebjada, S, Saw, S-M, Stambolian, D, Simpson, CL, Tai, E-S, Tideman, JWL, Tsujikawa, A, Vitart, V, Wang, N, Wedenoja, J, Wei, WB, Williams, C, Williams, KM, Wilson, JF, Wojciechowski, R, Wang, YX, Yamashiro, K, Yam, JCS, Yap, MKH, Yazar, S, Yip, SP, Young, TL, Zhou, X, Tedja, MS, Haarman, AEG, Meester-Smoor, MA, Kaprio, J, Mackey, DA, Guggenheim, JA, Hammond, CJ, Verhoeven, VJM, Klaver, CCW, Bailey-Wilson, JE, Baird, PN, Veluchamy, AB, Biino, G, Burdon, KP, Campbell, H, Chen, LJ, Cheng, C-Y, Chew, EY, Craig, JE, Cumberland, PM, Deangelis, MM, Delcourt, C, Ding, X, van Duijn, CM, Evans, DM, Fan, Q, Fossarello, M, Foster, PJ, Gharahkhani, P, Iglesias, AI, Guol, X, Haller, T, Han, X, Hayward, C, He, M, Hewitt, AW, Hoang, Q, Hysi, PG, Igo, RP, Iyengar, SK, Jonas, JB, Kahonen, M, Khawaja, AP, Klein, BE, Klein, R, Lass, JH, Lee, K, Lehtimaki, T, Lewis, D, Li, Q, Li, S-M, Lyytikainen, L-P, MacGregor, S, Martin, NG, Meguro, A, Metspalu, A, Middlebrooks, C, Miyake, M, Mizuki, N, Musolf, A, Nickels, S, Oexle, K, Pang, CP, Parssinen, O, Paterson, AD, Pfeiffer, N, Polasek, O, Rahi, JS, Raitakari, O, Rudan, I, Sahebjada, S, Saw, S-M, Stambolian, D, Simpson, CL, Tai, E-S, Tideman, JWL, Tsujikawa, A, Vitart, V, Wang, N, Wedenoja, J, Wei, WB, Williams, C, Williams, KM, Wilson, JF, Wojciechowski, R, Wang, YX, Yamashiro, K, Yam, JCS, Yap, MKH, Yazar, S, Yip, SP, Young, TL, and Zhou, X
Abstract: The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.
Published: 2019

13. Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration

Author: Waksmunski, AR, Grunin, M, Kinzy, TG, Igo, RP, Haines, JL, Bailey, JNC, Fritsche, LG, Igl, W, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, M, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Ouyang, H, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Stark, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-A, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, S, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, A, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Iyengar, SK, Weber, BHF, Abecasis, GR, Heid, IM, Waksmunski, AR, Grunin, M, Kinzy, TG, Igo, RP, Haines, JL, Bailey, JNC, Fritsche, LG, Igl, W, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, M, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Ouyang, H, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Stark, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-A, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, S, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, A, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Iyengar, SK, Weber, BHF, Abecasis, GR, and Heid, IM
Abstract: PURPOSE: Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS: We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS: We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) "drive" the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS: We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD.
Published: 2019

14. Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

Author: Iglesias Gonzalez, Adriana, Ong, JS, Khawaja, AP, Gharahkhani, P, Tedja, Milly, Verhoeven, Virginie, Bonnemaijer, Pieter, Wolfs, R.C.W., Young, TL, Jansonius, NM, Craig, JE, Stambolian, D, Duijn, Cornelia, Macgregor, S, Klaver, Caroline, Iglesias Gonzalez, Adriana, Ong, JS, Khawaja, AP, Gharahkhani, P, Tedja, Milly, Verhoeven, Virginie, Bonnemaijer, Pieter, Wolfs, R.C.W., Young, TL, Jansonius, NM, Craig, JE, Stambolian, D, Duijn, Cornelia, Macgregor, S, and Klaver, Caroline
Published: 2019

15. Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

Author: Tedja, MS, Wojciechowski, R, Hysi, PG, Eriksson, N, Furlotte, NA, Verhoeven, VJM, Iglesias, AI, Meester-Smoor, MA, Tompson, SW, Fan, Q, Khawaja, AP, Cheng, C-Y, Höhn, R, Yamashiro, K, Wenocur, A, Grazal, C, Haller, T, Metspalu, A, Wedenoja, J, Jonas, JB, Wang, YX, Xie, J, Mitchell, P, Foster, PJ, Klein, BEK, Klein, R, Paterson, AD, Hosseini, SM, Shah, RL, Williams, C, Teo, YY, Tham, YC, Gupta, P, Zhao, W, Shi, Y, Saw, W-Y, Tai, E-S, Sim, XL, Huffman, JE, Polašek, O, Hayward, C, Bencic, G, Rudan, I, Wilson, JF, Consortium, Cream, Team, 23Andme Research, Consortium, Uk Biobank Eye And Vision, Joshi, PK, Tsujikawa, A, Matsuda, F, Whisenhunt, KN, Zeller, T, Van Der Spek, PJ, Haak, R, Meijers-Heijboer, H, Van Leeuwen, EM, Iyengar, SK, Lass, JH, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Vingerling, JR, Lehtimäki, T, Raitakari, OT, Biino, G, Concas, MP, Schwantes-An, T-H, Igo, RP, Cuellar-Partida, G, Martin, NG, Craig, JE, Gharahkhani, P, Williams, KM, Nag, A, Rahi, JS, Cumberland, PM, Delcourt, C, Bellenguez, C, Ried, JS, Bergen, AA, Meitinger, T, Gieger, C, Wong, TY, Hewitt, AW, Mackey, DA, Simpson, CL, Pfeiffer, N, Pärssinen, O, Baird, PN, Vitart, V, Amin, N, Van Duijn, CM, Bailey-Wilson, JE, Young, TL, Saw, S-M, Stambolian, D, Macgregor, S, Guggenheim, JA, Tung, JY, Hammond, CJ, Klaver, CCW, Netherlands Institute for Neuroscience (NIN), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, Tedja, Milly S [0000-0003-0356-9684], Hysi, Pirro G [0000-0001-5752-2510], Verhoeven, Virginie JM [0000-0001-7359-7862], Iglesias, Adriana I [0000-0001-5532-764X], Tompson, Stuart W [0000-0001-9788-6730], Khawaja, Anthony P [0000-0001-6802-8585], Yamashiro, Kenji [0000-0001-9354-8558], Wedenoja, Juho [0000-0002-6155-0378], Jonas, Jost B [0000-0003-2972-5227], Wang, Ya Xing [0000-0003-2749-7793], Foster, Paul J [0000-0002-4755-177X], Klein, Ronald [0000-0002-4428-6237], Shah, Rupal L [0000-0001-8789-8869], Hayward, Caroline [0000-0002-9405-9550], Rudan, Igor [0000-0001-6993-6884], Wilson, James F [0000-0001-5751-9178], Joshi, Peter K [0000-0002-6361-5059], Whisenhunt, Kristina N [0000-0003-2412-7666], Rivadeneira, Fernando [0000-0001-9435-9441], Biino, Ginevra [0000-0002-9936-946X], Gharahkhani, Puya [0000-0002-4203-5952], Williams, Katie M [0000-0003-4596-3938], Delcourt, Cécile [0000-0002-2099-0481], Bellenguez, Céline [0000-0002-1240-7874], Hewitt, Alex W [0000-0002-5123-5999], Baird, Paul N [0000-0002-1305-3502], Bailey-Wilson, Joan E [0000-0002-9153-2920], Young, Terri L [0000-0001-6994-9941], Guggenheim, Jeremy A [0000-0001-5164-340X], Hammond, Christopher J [0000-0002-3227-2620], Klaver, Caroline CW [0000-0002-2355-5258], Apollo - University of Cambridge Repository, Epidemiology, Ophthalmology, Clinical Genetics, Pathology, Internal Medicine, Graduate School, Human Genetics, Experimental Immunology, ANS - Complex Trait Genetics, and ARD - Amsterdam Reproduction and Development
Subjects: 0301 basic medicine, Adult, Male, Cell type, ResearchInstitutes_Networks_Beacons/MICRA, In silico, taittovirheet, Genome-wide association study, Retinal Pigment Epithelium, Biology, Blindness, Polymorphism, Single Nucleotide, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, Retina, White People, 03 medical and health sciences, HIGH-GRADE MYOPIA, RETINAL-PIGMENT EPITHELIUM, SEROTONIN PATHWAY GENES, FORM-DEPRIVATION MYOPIA, COMMON VARIANTS, OCULAR GROWTH, RETINITIS-PIGMENTOSA, GENOTYPE IMPUTATION, MISSENSE MUTATIONS, DOPAMINE-RECEPTORS, Asian People, refractive errors, Retinitis pigmentosa, Genetics, medicine, Myopia, Journal Article, Humans, Genetic Predisposition to Disease, 610 Medicine & health, Regulation of gene expression, Retinal pigment epithelium, medicine.disease, Refractive Errors, 030104 developmental biology, medicine.anatomical_structure, Manchester Institute for Collaborative Research on Ageing, Gene Expression Regulation, genetic factors, Eye disorder, Female, sense organs, geneettiset tekijät, Neuroscience, Genome-Wide Association Study, Signal Transduction
Abstract: Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach. Keratinocyte (HaCaT) mono-cultures (MoC) or HaCaT/THP-1 co-cultures (CoC) were challenged with 100, 200 or 300 mM SM for 1 h. Post-exposure, both MoC and CoC were treated with 10, 30 or 50 mu M BER for 24 h. At that time, supernatants were collected and analyzed both for interleukine (IL) 6 and 8 levels and for content of adenylate-kinase (AK) as surrogate marker for cell necrosis. Cells were lysed and nucleosome formation as marker for late apoptosis was assessed. In parallel, AK in cells was determined for normalization purposes. BER treatment did not influence necrosis, but significantly decreased apoptosis. Anti-inflammatory effects were moderate, but also significant, primarily in CoC. Overall, BER has protective effects against SM toxicity in vitro. Whether this holds true should be evaluated in future in vivo studies.
Published: 2018

16. Exclusion of three candidate genes, Grpr, Cxn33, and Pdha1, for the X-linked cataract gene on the distal region of the mouse Chromosome X

Author: Zhou, E., Favor, J., Silvers, W., and Stambolian, D.
Published: 1995
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17. Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

Author: Tedja, M.S., Wojciechowski, R., Hysi, P.G., Eriksson, N., Furlotte, N.A., Verhoeven, V.J., Iglesias, A.I., Meester-Smoor, M.A., Tompson, S.W., Fan, Q., Khawaja, A.P., Cheng, C.Y., Hohn, R., Yamashiro, K., Wenocur, A., Grazal, C., Haller, T., Metspalu, A., Wedenoja, J., Jonas, J.B., Wang, Y.X., Xie, J, Mitchell, P., Foster, P.J., Klein, B.E., Klein, R., Paterson, A.D., Hosseini, S.M., Shah, R.L., Williams, C., Teo, Y.Y., Tham, Y.C., Gupta, P., Zhao, W., Shi, Yuan, Saw, W.Y., Tai, E.S., Sim, X.L., Huffman, J.E., Polasek, O., Hayward, C., Bencic, G., Rudan, I., Wilson, J.F., Joshi, P.K., Tsujikawa, A., Matsuda, F., Whisenhunt, K.N., Zeller, T., Spek, P.J. van der, Haak, R., Meijers-Heijboer, H., Leeuwen, E.M. van, Iyengar, S.K., Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Jr., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Nag, A., Rahi, J.S., Cumberland, P.M., Delcourt, C, Bellenguez, C., Ried, J.S., Bergen, A.A., Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Duijn, C.M. van, Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., Klaver, C.C.W., Tedja, M.S., Wojciechowski, R., Hysi, P.G., Eriksson, N., Furlotte, N.A., Verhoeven, V.J., Iglesias, A.I., Meester-Smoor, M.A., Tompson, S.W., Fan, Q., Khawaja, A.P., Cheng, C.Y., Hohn, R., Yamashiro, K., Wenocur, A., Grazal, C., Haller, T., Metspalu, A., Wedenoja, J., Jonas, J.B., Wang, Y.X., Xie, J, Mitchell, P., Foster, P.J., Klein, B.E., Klein, R., Paterson, A.D., Hosseini, S.M., Shah, R.L., Williams, C., Teo, Y.Y., Tham, Y.C., Gupta, P., Zhao, W., Shi, Yuan, Saw, W.Y., Tai, E.S., Sim, X.L., Huffman, J.E., Polasek, O., Hayward, C., Bencic, G., Rudan, I., Wilson, J.F., Joshi, P.K., Tsujikawa, A., Matsuda, F., Whisenhunt, K.N., Zeller, T., Spek, P.J. van der, Haak, R., Meijers-Heijboer, H., Leeuwen, E.M. van, Iyengar, S.K., Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Jr., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Nag, A., Rahi, J.S., Cumberland, P.M., Delcourt, C, Bellenguez, C., Ried, J.S., Bergen, A.A., Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Duijn, C.M. van, Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., and Klaver, C.C.W.
Abstract: Item does not contain fulltext, Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.
Published: 2018

18. Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

Author: Tedja, Milly S, Wojciechowski, Robert, Hysi, Pirro G, Eriksson, Nicholas, Furlotte, Nicholas A, Verhoeven, Virginie J M, Iglesias, Adriana I, Meester-Smoor, Magda A, Tompson, Stuart W, Fan, Qiao, Khawaja, Anthony P, Cheng, Ching-Yu, Höhn, René, Yamashiro, Kenji, Wenocur, Adam, Grazal, Clare, Haller, Toomas, Metspalu, Andres, Wedenoja, Juho, Jonas, Jost B, Wang, Ya Xing, Xie, Jing, Mitchell, Paul, Foster, Paul J, Klein, Barbara E K, Klein, Ronald, Paterson, Andrew D, Hosseini, S Mohsen, Shah, Rupal L, Williams, Cathy, Teo, Yik-Ying, Tham, Yih Chung, Gupta, Preeti, Zhao, Wanting, Shi, Yuan, Saw, Woei-Yuh, Tai, E-Shyong, Sim, Xue Ling, Huffman, Jennifer E, Polašek, Ozren, Hayward, Caroline, Bencic, Goran, Rudan, Igor, Wilson, James F, CREAM Consortium, Joshi, Peter K, Tsujikawa, Akitaka, Matsuda, Fumihiko, Whisenhunt, Kristina N, Zeller, Tanja, Van der Spek, P.J., Haak, R., Meijers-Heijboer, Hanne, van Leeuwen, Elisabeth M, Iyengar, Sudha K, Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Naq, A., Rahi, J.S., Cumberland, P.M., Delcourt, C., Bellenquez, C., Ried, J.S., Bergen, Arthur A, Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Van Duijn, C.M., Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., Klaver, C.C.W., Tedja, Milly S, Wojciechowski, Robert, Hysi, Pirro G, Eriksson, Nicholas, Furlotte, Nicholas A, Verhoeven, Virginie J M, Iglesias, Adriana I, Meester-Smoor, Magda A, Tompson, Stuart W, Fan, Qiao, Khawaja, Anthony P, Cheng, Ching-Yu, Höhn, René, Yamashiro, Kenji, Wenocur, Adam, Grazal, Clare, Haller, Toomas, Metspalu, Andres, Wedenoja, Juho, Jonas, Jost B, Wang, Ya Xing, Xie, Jing, Mitchell, Paul, Foster, Paul J, Klein, Barbara E K, Klein, Ronald, Paterson, Andrew D, Hosseini, S Mohsen, Shah, Rupal L, Williams, Cathy, Teo, Yik-Ying, Tham, Yih Chung, Gupta, Preeti, Zhao, Wanting, Shi, Yuan, Saw, Woei-Yuh, Tai, E-Shyong, Sim, Xue Ling, Huffman, Jennifer E, Polašek, Ozren, Hayward, Caroline, Bencic, Goran, Rudan, Igor, Wilson, James F, CREAM Consortium, Joshi, Peter K, Tsujikawa, Akitaka, Matsuda, Fumihiko, Whisenhunt, Kristina N, Zeller, Tanja, Van der Spek, P.J., Haak, R., Meijers-Heijboer, Hanne, van Leeuwen, Elisabeth M, Iyengar, Sudha K, Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Naq, A., Rahi, J.S., Cumberland, P.M., Delcourt, C., Bellenquez, C., Ried, J.S., Bergen, Arthur A, Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Van Duijn, C.M., Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., and Klaver, C.C.W.
Abstract: Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.
Published: 2018

19. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis

Author: Bourne, RRA, Flaxman, SR, Braithwaite, T, Cicinelli, MV, Das, A, Jonas, JB, Keeffe, J, Kempen, JH, Leasher, J, Limburg, H, Naidoo, K, Pesudovs, K, Resnikoff, S, Silvester, A, Stevens, GA, Tahhan, N, Wong, TY, Taylor, HR, Ackland, P, Arditi, A, Barkana, Y, Bozkurt, B, Wormald, R, Bron, A, Budenz, D, Cai, F, Casson, R, Chakravarthy, U, Congdon, N, Peto, T, Choi, J, Dana, R, Palaiou, M, Dandona, R, Dandona, L, Shen, T, Dekaris, I, Del Monte, M, Deva, J, Dreer, L, Frazier, M, Ellwein, L, Hejtmancik, J, Frick, K, Friedman, D, Javitt, J, Munoz, B, Quigley, H, Ramulu, P, Robin, A, Tielsch, J, West, S, Furtado, J, Gao, H, Gazzard, G, George, R, Gichuhi, S, Gonzalez, V, Hammond, B, Hartnett, ME, He, M, Hirai, F, Huang, J, Ingram, A, Joslin, C, Khanna, R, Stambolian, D, Khairallah, M, Kim, J, Lambrou, G, Lansingh, VC, Lanzetta, P, Lim, J, Mansouri, K, Mathew, A, Morse, A, Musch, D, Nangia, V, Battaglia, M, Yaacov, F, Raju, M, Rossetti, L, Saaddine, J, Sandar, M, Serle, J, Shetty, R, Sieving, P, Silva, JC, Sitorus, RS, Tejedor, J, Tsilimbaris, M, Bourne, RRA, Flaxman, SR, Braithwaite, T, Cicinelli, MV, Das, A, Jonas, JB, Keeffe, J, Kempen, JH, Leasher, J, Limburg, H, Naidoo, K, Pesudovs, K, Resnikoff, S, Silvester, A, Stevens, GA, Tahhan, N, Wong, TY, Taylor, HR, Ackland, P, Arditi, A, Barkana, Y, Bozkurt, B, Wormald, R, Bron, A, Budenz, D, Cai, F, Casson, R, Chakravarthy, U, Congdon, N, Peto, T, Choi, J, Dana, R, Palaiou, M, Dandona, R, Dandona, L, Shen, T, Dekaris, I, Del Monte, M, Deva, J, Dreer, L, Frazier, M, Ellwein, L, Hejtmancik, J, Frick, K, Friedman, D, Javitt, J, Munoz, B, Quigley, H, Ramulu, P, Robin, A, Tielsch, J, West, S, Furtado, J, Gao, H, Gazzard, G, George, R, Gichuhi, S, Gonzalez, V, Hammond, B, Hartnett, ME, He, M, Hirai, F, Huang, J, Ingram, A, Joslin, C, Khanna, R, Stambolian, D, Khairallah, M, Kim, J, Lambrou, G, Lansingh, VC, Lanzetta, P, Lim, J, Mansouri, K, Mathew, A, Morse, A, Musch, D, Nangia, V, Battaglia, M, Yaacov, F, Raju, M, Rossetti, L, Saaddine, J, Sandar, M, Serle, J, Shetty, R, Sieving, P, Silva, JC, Sitorus, RS, Tejedor, J, and Tsilimbaris, M
Abstract: © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (−36·7%). T
Published: 2017

20. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis

Author: Flaxman, SR, Bourne, RRA, Resnikoff, S, Ackland, P, Braithwaite, T, Cicinelli, MV, Das, A, Jonas, JB, Keeffe, J, Kempen, JH, Leasher, J, Limburg, H, Naidoo, K, Pesudovs, K, Silvester, A, Stevens, GA, Tahhan, N, Wong, TY, Taylor, HR, Arditi, A, Barkana, Y, Bozkurt, B, Bron, A, Budenz, D, Cai, F, Casson, R, Chakravarthy, U, Choi, J, Congdon, N, Dana, R, Dandona, R, Dandona, L, Dekaris, I, Del Monte, M, Deva, J, Dreer, L, Ellwein, L, Frazier, M, Frick, K, Friedman, D, Furtado, J, Gao, H, Gazzard, G, George, R, Gichuhi, S, Gonzalez, V, Hammond, B, Hartnett, ME, He, M, Hejtmancik, J, Hirai, F, Huang, J, Ingram, A, Javitt, J, Joslin, C, Khairallah, M, Khanna, R, Kim, J, Lambrou, G, Lansingh, VC, Lanzetta, P, Lim, J, Mansouri, K, Mathew, A, Morse, A, Munoz, B, Musch, D, Nangia, V, Palaiou, M, Parodi, MB, Pena, FY, Peto, T, Quigley, H, Raju, M, Ramulu, P, Reza, D, Robin, A, Rossetti, L, Saaddine, J, Sandar, M, Serle, J, Shen, T, Shetty, R, Sieving, P, Silva, JC, Sitorus, RS, Stambolian, D, Tejedor, J, Tielsch, J, Tsilimbaris, M, van Meurs, J, Flaxman, SR, Bourne, RRA, Resnikoff, S, Ackland, P, Braithwaite, T, Cicinelli, MV, Das, A, Jonas, JB, Keeffe, J, Kempen, JH, Leasher, J, Limburg, H, Naidoo, K, Pesudovs, K, Silvester, A, Stevens, GA, Tahhan, N, Wong, TY, Taylor, HR, Arditi, A, Barkana, Y, Bozkurt, B, Bron, A, Budenz, D, Cai, F, Casson, R, Chakravarthy, U, Choi, J, Congdon, N, Dana, R, Dandona, R, Dandona, L, Dekaris, I, Del Monte, M, Deva, J, Dreer, L, Ellwein, L, Frazier, M, Frick, K, Friedman, D, Furtado, J, Gao, H, Gazzard, G, George, R, Gichuhi, S, Gonzalez, V, Hammond, B, Hartnett, ME, He, M, Hejtmancik, J, Hirai, F, Huang, J, Ingram, A, Javitt, J, Joslin, C, Khairallah, M, Khanna, R, Kim, J, Lambrou, G, Lansingh, VC, Lanzetta, P, Lim, J, Mansouri, K, Mathew, A, Morse, A, Munoz, B, Musch, D, Nangia, V, Palaiou, M, Parodi, MB, Pena, FY, Peto, T, Quigley, H, Raju, M, Ramulu, P, Reza, D, Robin, A, Rossetti, L, Saaddine, J, Sandar, M, Serle, J, Shen, T, Shetty, R, Sieving, P, Silva, JC, Sitorus, RS, Stambolian, D, Tejedor, J, Tielsch, J, Tsilimbaris, M, and van Meurs, J
Abstract: © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. Methods In this systematic review and meta-analysis, we analysed published and unpublished population-based data for the causes of vision impairment and blindness from 1980 to 2014. We identified population-based studies published before July 8, 2014, by searching online databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression models to estimate the proportion of moderate or severe vision impairment (defined as presenting visual acuity of <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity of <3/60 in the better eye) by cause, age, region, and year. Findings We identified 288 studies of 3 983 541 participants contributing data from 98 countries. Among the global population with moderate or severe vision impairment in 2015 (216·6 million [80% uncertainty interval 98·5 million to 359·1 million]), the leading causes were uncorrected refractive error (116·3 million [49·4 million to 202·1 million]), cataract (52·6 million [18·2 million to 109·6 million]), age-related macular degeneration (8·4 million [0·9 million to 29·5 million]), glaucoma (4·0 million [0·6 million to 13·3 million]), and diabetic retinopathy (2·6 million [0·2 million to 9·9 million]). Among the global population who were blind in 2015 (36·0 million [12·9 million to 65·4 million]), the leading causes were cataract (12·6 million [3·4 million to 28·7 million]), uncorrected refractive error (7·4 million [2·4 million to 14·8 million]), a
Published: 2017

21. Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy

Author: Afshari, NA, Igo, RP, Morris, NJ, Stambolian, D, Sharma, S, Pulagam, VL, Dunn, S, Stamler, JF, Truitt, BJ, Rimmler, J, Kuot, A, Croasdale, CR, Qin, X, Burdon, KP, Riazuddin, SA, Mills, R, Klebe, S, Minear, MA, Zhao, J, Balajonda, E, Rosenwasser, GO, Baratz, KH, Mootha, VV, Patel, SV, Gregory, SG, Bailey-Wilson, JE, Price, MO, Price, FW, Craig, JE, Fingert, JH, Gottsch, JD, Aldave, AJ, Klintworth, GK, Lass, JH, Li, Y-J, Iyengar, SK, Afshari, NA, Igo, RP, Morris, NJ, Stambolian, D, Sharma, S, Pulagam, VL, Dunn, S, Stamler, JF, Truitt, BJ, Rimmler, J, Kuot, A, Croasdale, CR, Qin, X, Burdon, KP, Riazuddin, SA, Mills, R, Klebe, S, Minear, MA, Zhao, J, Balajonda, E, Rosenwasser, GO, Baratz, KH, Mootha, VV, Patel, SV, Gregory, SG, Bailey-Wilson, JE, Price, MO, Price, FW, Craig, JE, Fingert, JH, Gottsch, JD, Aldave, AJ, Klintworth, GK, Lass, JH, Li, Y-J, and Iyengar, SK
Abstract: The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.
Published: 2017

22. Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study

Author: Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW, Williams, C, Wang, JJ, Kho, P-F, Saw, SM, Cheng, C-Y, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, P, Hammond, CJ, Mackey, DA, Lucas, RM, MacGregor, S, Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW, Williams, C, Wang, JJ, Kho, P-F, Saw, SM, Cheng, C-Y, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, P, Hammond, CJ, Mackey, DA, Lucas, RM, and MacGregor, S
Abstract: BACKGROUND: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia. METHODS: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS. RESULTS: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians. CONCLUSIONS: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors.
Published: 2017

23. Imaging Lenticular Autofluorescence in Older Subjects

Author: Charng, J, Tan, R, Luu, CD, Sadigh, S, Stambolian, D, Guymer, RH, Jacobson, SG, Cideciyan, AV, Charng, J, Tan, R, Luu, CD, Sadigh, S, Stambolian, D, Guymer, RH, Jacobson, SG, and Cideciyan, AV
Abstract: PURPOSE: To evaluate whether a practical method of imaging lenticular autofluorescence (AF) can provide an individualized measure correlated with age-related lens yellowing in older subjects undergoing tests involving shorter wavelength lights. METHODS: Lenticular AF was imaged with 488-nm excitation using a confocal scanning laser ophthalmoscope (cSLO) routinely used for retinal AF imaging. There were 75 older subjects (ages 47-87) at two sites; a small cohort of younger subjects served as controls. At one site, the cSLO was equipped with an internal reference to allow quantitative AF measurements; at the other site, reduced-illuminance AF imaging (RAFI) was used. In a subset of subjects, lens density index was independently estimated from dark-adapted spectral sensitivities performed psychophysically. RESULTS: Lenticular AF intensity was significantly higher in the older eyes than the younger cohort when measured with the internal reference (59.2 ± 15.4 vs. 134.4 ± 31.7 gray levels; P < 0.05) as well as when recorded with RAFI without the internal reference (10.9 ± 1.5 vs. 26.1 ± 5.7 gray levels; P < 0.05). Lenticular AF was positively correlated with age; however, there could also be large differences between individuals of similar age. Lenticular AF intensity correlated well with lens density indices estimated from psychophysical measures. CONCLUSIONS: Lenticular AF measured with a retinal cSLO can provide a practical and individualized measure of lens yellowing, and may be a good candidate to distinguish between preretinal and retinal deficits involving short-wavelength lights in older eyes.
Published: 2017

24. Assessing the genetic predisposition of education on myopia: A mendelian randomization study

Author: Cuellar-Partida, G., Lu, Y., Kho, P.F., Hewitt, A.W., Wichmann, H.-E., Yazar, S., Stambolian, D., Bailey-Wilson, J.E., Wojciechowski, R., Wang, J.J., Mitchell, P., Mackey, D.A., and MacGregor, S.
Subjects: Education, Instrumental Variable, Mendelian Randomization, Myopia, Polygenic Risk Scores, Refractive Error, genetic structures
Abstract: Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10-3). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error.
Published: 2016

25. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author: Fan, Q., Guo, X., Tideman, J.W.L., Williams, K.M., Yazar, S., Hosseini, S.M., Howe, L.D., Pourcain, B.S., Evans, D.M., Timpson, N.J., McMahon, G., Hysi, P.G., Krapohl, E., Wang, Y.X., Jonas, J.B., Baird, P.N., Wang, J.J., Cheng, C.Y., Teo, Y.Y., Wong, T.Y., Ding, X., Wojciechowski, R., Young, T.L., Pärssinen, O., Oexle, K., Pfeiffer, N., Bailey-Wilson, J.E., Paterson, A.D., Klaver, C.C.W., Plomin, R., Hammond, C.J., He, M., Saw, S.M., Guggenheim, J.A., Meguro, A., Wright, A.F., Hewitt, A.W., Young, A.L., Veluchamy, A.B., Metspalu, A., The CREAM Consortium (Döring, A., Gieger, C., Ried, J.S.), Khawaja, A.P., Klein, B.E., St Pourcain, B., Fleck, B., Hayward, C., Williams, C., Delcourt, C., Pang, C.P., Khor, C.C., Simpson, C.L., van Duijn, C.M., Mackey, D.A., Stambolian, D., Chew, E., Tai, E.S., Mihailov, E., Smith, G.D., Biino, G., Campbell, H., Rudan, I., Seppälä, I., Kaprio, J., Wilson, J.F., and Craig, J.E.
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
Published: 2016

26. The mouse Cat4 locus maps to Chromosome 8 and mutants express lens-corneal adhesion

Author: Favor, J., Grimes, P., Neuhäuser-Klaus, A., Pretsch, W., and Stambolian, D.
Published: 2008
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27. Age-related macular degeneration-associated variants at chromosome 10q26 do not significantly alter ARMS2 and HTRA1 transcript levels in the human retina

Author: Kanda, A., Stambolian, D., Chen, W., Curcio, C. A., Abecasis, G. R., and Anand Swaroop
Subjects: Adult, Genotype, Chromosomes, Human, Pair 10, Placenta, Serine Endopeptidases, Proteins, High-Temperature Requirement A Serine Peptidase 1, eye diseases, Retina, Macular Degeneration, Gene Expression Regulation, Pregnancy, Mutation, Humans, Female, sense organs, RNA, Messenger, Research Article, Aged
Abstract: Purpose Multiple studies demonstrate a strong association between three variants at chromosome 10q26 – rs10490924, del443ins54, and rs11200638 – near the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HTRA1) genes with susceptibility to age-related macular degeneration (AMD). In different reports, the del443ins54 and rs11200638 variants are suggested to affect ARMS2 mRNA stability and/or HTRA1 mRNA expression, respectively. The goal of this study is to examine whether these AMD-associated variants alter expression levels of ARMS2 and HTRA1 in human retina samples. Methods Genomic DNA and total RNA were obtained from 35 human retinas (three young controls, average age=32 years; twenty aged controls, average age=72 years; and twelve AMD retinas, average age=77 years) using standard procedures. As ARMS2 exhibits higher expression in the human placenta, we also included eighteen placenta samples in our analysis. Four polymorphisms – rs2736911, rs10490924, del443ins54, and rs11200638 – were genotyped by PCR followed by sequencing. Expression of ARMS2, HTRA1 and three endogenous control genes (rRNA [rRNA], hypoxanthine phosphoribosyltransferase 1 [HPRT1], and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) was measured by real-time quantitative RT–PCR using Taqman gene expression or SYBR Green assays. Results ARMS2 and HTRA1 mRNA levels did not show a significant difference in expression among the control (young and elderly) and AMD retinas. No association of del443ins54 and rs11200638 variants was detected with mRNA expression levels of ARMS2 or HTRA1 in the retina. Human placenta samples showed high variability in expression levels. Conclusions We did not find association between AMD susceptibility variants at 10q26 and steady-state expression levels of either ARMS2 or HTRA1 in the human retina.
Published: 2010

28. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q., Verhoeven, V.J., Wojciechowski, R., Barathi, V.A., Hysi, P.G., Guggenheim, J.A., Hohn, R., Vitart, V., Khawaja, A.P., Yamashiro, K., Hosseini, S.M., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C, Pirastu, M., Wedenoja, J., Gharahkhani, P., Venturini, C., Miyake, M., Hewitt, A.W., Guo, X., Mazur, J., Huffman, J.E., Williams, K.M., Polasek, O., Campbell, H., Rudan, I., Vatavuk, Z., Wilson, J.F., Joshi, P.K., McMahon, G., St Pourcain, B., Evans, D.M., Simpson, C.L., Schwantes-An, T.H., Igo, R.P., Jr., Mirshahi, A., Cougnard-Gregoire, A., Bellenguez, C., Blettner, M., Raitakari, O., Kahonen, M., Seppala, I., Zeller, T., Meitinger, T., Ried, J.S., Gieger, C., Portas, L., Leeuwen, E.M. van, Amin, N., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., Vingerling, J.R., Wang, Y.X., Wang, X., Boh, E.T.H., Ikram, M.K., Sabanayagam, C., Gupta, P., Tan, V., Zhou, L, Ho, C.E., Lim, W., Beuerman, R.W., Siantar, R., Tai, E.S., Vithana, E., Mihailov, E., Khor, C.C., Hayward, C., Luben, R.N., Foster, P.J., Klein, B.E., Klein, R., Wong, H.S., Mitchell, P., Metspalu, A., Aung, T., Young, T.L., He, M., Parssinen, O., Duijn, C.M. van, Wang, J.J., Williams, C., Jonas, J.B., Teo, Y.Y., Mackey, D.A., Oexle, K., Yoshimura, N., Paterson, A.D., Pfeiffer, N., Wong, T.Y., Baird, P.N., Stambolian, D., Wilson, J.E., Cheng, C.Y., Hammond, C.J., Klaver, C.C.W., et al., Fan, Q., Verhoeven, V.J., Wojciechowski, R., Barathi, V.A., Hysi, P.G., Guggenheim, J.A., Hohn, R., Vitart, V., Khawaja, A.P., Yamashiro, K., Hosseini, S.M., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C, Pirastu, M., Wedenoja, J., Gharahkhani, P., Venturini, C., Miyake, M., Hewitt, A.W., Guo, X., Mazur, J., Huffman, J.E., Williams, K.M., Polasek, O., Campbell, H., Rudan, I., Vatavuk, Z., Wilson, J.F., Joshi, P.K., McMahon, G., St Pourcain, B., Evans, D.M., Simpson, C.L., Schwantes-An, T.H., Igo, R.P., Jr., Mirshahi, A., Cougnard-Gregoire, A., Bellenguez, C., Blettner, M., Raitakari, O., Kahonen, M., Seppala, I., Zeller, T., Meitinger, T., Ried, J.S., Gieger, C., Portas, L., Leeuwen, E.M. van, Amin, N., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., Vingerling, J.R., Wang, Y.X., Wang, X., Boh, E.T.H., Ikram, M.K., Sabanayagam, C., Gupta, P., Tan, V., Zhou, L, Ho, C.E., Lim, W., Beuerman, R.W., Siantar, R., Tai, E.S., Vithana, E., Mihailov, E., Khor, C.C., Hayward, C., Luben, R.N., Foster, P.J., Klein, B.E., Klein, R., Wong, H.S., Mitchell, P., Metspalu, A., Aung, T., Young, T.L., He, M., Parssinen, O., Duijn, C.M. van, Wang, J.J., Williams, C., Jonas, J.B., Teo, Y.Y., Mackey, D.A., Oexle, K., Yoshimura, N., Paterson, A.D., Pfeiffer, N., Wong, T.Y., Baird, P.N., Stambolian, D., Wilson, J.E., Cheng, C.Y., Hammond, C.J., Klaver, C.C.W., and et al.
Abstract: Contains fulltext : 167942.pdf (publisher's version ) (Open Access), Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP x education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 x 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016

29. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Author: Fritsche, L.G. (Lars), Igl, W. (Wilmar), Cooke Bailey, J.N. (Jessica N.), Grassmann, F. (Felix), Sengupta, S. (Sebanti), Bragg-Gresham, J.L. (Jennifer L.), Burdon, K.P. (Kathryn P.), Hebbring, S.J. (Scott J.), Wen, C. (Cindy), Gorski, M. (Mathias), Kim, I.K. (Ivana), Cho, D. (David), Zack, D. (Donald), Souied, E.H. (Eric), Scholl, H.P.N. (Hendrik), Bala, E. (Elisa), ELee, K. (Kristine), Hunter, D. (David), Sardell, R.J. (Rebecca J.), Mitchell, P. (Paul), Merriam, J.E. (Joanna), Cipriani, F. (Francesco), Hoffman, J.D. (Joshua D.), Schick, T. (Tina), Lechanteur, Y.T.E. (Yara T. E.), Guymer, R.H. (Robyn), Johnson, M.P. (Matthew), Jiang, Y., Stanton, C.M. (Chloe), Buitendijk, G.H.S. (Gabrielle), Zhan, X. (Xiaowei), Kwong, A.M. (Alan M.), Boleda, A. (Alexis), Brooks, M. (Matthew), Gieser, L. (Linn), Ratna Priya, R. (Rinki), Branham, K.E. (Kari), Foerster, J.R. (Johanna R.), Heckenlively, J.R. (John), Othman, M.I. (Mohammad), Vote, B.J. (Brendan J.), Liang, H.H. (Helena Hai), Souzeau, E. (Emmanuelle), McAllister, I.L. (Ian L.), Isaacs, T. (Timothy), Hall, J. (Janette), Lake, S. (Stewart), Mackey, D.A. (David), Constable, I.J. (Ian J.), Craig, J.E. (Jamie E.), Kitchner, T.E. (Terrie E.), Yang, Z. (Zhenglin), Su, Z. (Zhiguang), Luo, H. (Hongrong), Chen, D. (Daniel), Ouyang, H. (Hong), Flagg, K. (Ken), Lin, D. (Danni), Mao, G. (Guanping), Ferreyra, H.A. (Henry), Stark, K. (Klaus), Strachwitz, C. (Claudia) von, Wolf, A. (Armin), Brandl, C. (Caroline), Rudolph, G. (Guenther), Olden, M. (Matthias), Morrison, M.A. (Margaux), Morgan, D.J. (Denise), Schu, M. (Matthew), Ahn, J. (Jeeyun), Silvestri, G. (Giuliana), Tsironi, E.E. (Evangelia), Park, K.H. (Kyu Hyung), Farrer, L.A. (Lindsay), Orlin, A. (Anton), Brucker, A. (Alexander), Curcio, C.A. (Christine A.), Mohand-Sa'd, S. (Saddek), Sahel, J.-A. (José-Alain), Audo, I. (Isabelle), Benchaboune, M. (Mustapha), Cree, A.J. (Angela), Rennie, C.A. (Christina A.), Goverdhan, S.V. (Srinivas V.), Grunin, M. (Michelle), Hagbi-Levi, S. (Shira), Campochiaro, B. (Betsy), Katsanis, N. (Nicholas), Holz, F.G. (Frank), Blond, F. (Frédéric), Blanché, H. (Hél'ne), Deleuze, J.-F. (Jean-Fran'ois), Igo Jr., R.P. (Robert), Truitt, B.J. (Barbara), Peachey, N.S. (Neal ), Meuer, S.M. (Stacy), Myers, C.E. (Chelsea), Moore, E.L. (Emily L.), Klein, R. (Ronald), Hauser, M.A. (Michael), Postel, E.A. (Eric), Courtenay, M.D. (Monique D.), Schwartz, S.M. (Stephen), Kovach, J.L. (Jaclyn), Scott, W.K. (William), Liew, G. (Gerald), Tan, A.G. (Ava G.), Gopinath, B. (Bamini), Smith, T. (Tim), Khan, J.C. (Jane), Shahid, M. (Mohammad), Moore, A.T. (Anthony), McGrath, J.A. (J Allie), Laux, R. (Reneé), Brantley, M.A. (Milam), Agarwal, A. (Anita), Ersoy, L. (Lebriz), Caramoy, A. (Albert), Langmann, T. (Thomas), Saksens, N.T.M. (Nicole T.), Jong, E.K. (Eiko Kde), Hoyng, C.B. (Carel), Cain, M.S. (Melinda), Richardson, A.J. (Andrea), Martin, T.M. (Tammy M.), Blangero, J. (John), Weeks, D.E. (Daniel), Dhillon, B. (Bal), Duijn, C.M. (Cornelia) van, Doheny, K.F. (Kimberly), Romm, J. (Jane), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Gorin, M.B. (Michael B.), Klein, M.L. (Michael), Baird, P.N. (Paul), Hollander, A.I. (Anneke), Fauser, S. (Sascha), WYates, J.R. (John R.), Allikmets, R. (Rando), Wang, J.J. (Jie Jin), Schaumberg, D.A. (Debra), Klein, B.E.K. (Barbara), Hagstrom, S.A. (Stephanie), Chowers, Y. (Yehuda), Lotery, A.J. (Andrew), Léveillard, T. (Thierry), Zhang, K. (Kang), Brilliant, M.H. (Murray H.), Hewit, A.W. (Alex), Swaroop, A. (Anand), Chew, E.Y. (Emily Y.), Pericak-Vance, M.A. (Margaret), DeAngelis, M.M. (Margaret), Stambolian, D. (Dwight), Haines, J.L. (Jonathan), Iyengar, S.K. (Sudha), Weber, B.H.F. (Bernhard), Abecasis, G.R. (Gonçalo), Heid, I.M. (Iris), Li, M. (Mingyao), Fritsche, L.G. (Lars), Igl, W. (Wilmar), Cooke Bailey, J.N. (Jessica N.), Grassmann, F. (Felix), Sengupta, S. (Sebanti), Bragg-Gresham, J.L. (Jennifer L.), Burdon, K.P. (Kathryn P.), Hebbring, S.J. (Scott J.), Wen, C. (Cindy), Gorski, M. (Mathias), Kim, I.K. (Ivana), Cho, D. (David), Zack, D. (Donald), Souied, E.H. (Eric), Scholl, H.P.N. (Hendrik), Bala, E. (Elisa), ELee, K. (Kristine), Hunter, D. (David), Sardell, R.J. (Rebecca J.), Mitchell, P. (Paul), Merriam, J.E. (Joanna), Cipriani, F. (Francesco), Hoffman, J.D. (Joshua D.), Schick, T. (Tina), Lechanteur, Y.T.E. (Yara T. E.), Guymer, R.H. (Robyn), Johnson, M.P. (Matthew), Jiang, Y., Stanton, C.M. (Chloe), Buitendijk, G.H.S. (Gabrielle), Zhan, X. (Xiaowei), Kwong, A.M. (Alan M.), Boleda, A. (Alexis), Brooks, M. (Matthew), Gieser, L. (Linn), Ratna Priya, R. (Rinki), Branham, K.E. (Kari), Foerster, J.R. (Johanna R.), Heckenlively, J.R. (John), Othman, M.I. (Mohammad), Vote, B.J. (Brendan J.), Liang, H.H. (Helena Hai), Souzeau, E. (Emmanuelle), McAllister, I.L. (Ian L.), Isaacs, T. (Timothy), Hall, J. (Janette), Lake, S. (Stewart), Mackey, D.A. (David), Constable, I.J. (Ian J.), Craig, J.E. (Jamie E.), Kitchner, T.E. (Terrie E.), Yang, Z. (Zhenglin), Su, Z. (Zhiguang), Luo, H. (Hongrong), Chen, D. (Daniel), Ouyang, H. (Hong), Flagg, K. (Ken), Lin, D. (Danni), Mao, G. (Guanping), Ferreyra, H.A. (Henry), Stark, K. (Klaus), Strachwitz, C. (Claudia) von, Wolf, A. (Armin), Brandl, C. (Caroline), Rudolph, G. (Guenther), Olden, M. (Matthias), Morrison, M.A. (Margaux), Morgan, D.J. (Denise), Schu, M. (Matthew), Ahn, J. (Jeeyun), Silvestri, G. (Giuliana), Tsironi, E.E. (Evangelia), Park, K.H. (Kyu Hyung), Farrer, L.A. (Lindsay), Orlin, A. (Anton), Brucker, A. (Alexander), Curcio, C.A. (Christine A.), Mohand-Sa'd, S. (Saddek), Sahel, J.-A. (José-Alain), Audo, I. (Isabelle), Benchaboune, M. (Mustapha), Cree, A.J. (Angela), Rennie, C.A. (Christina A.), Goverdhan, S.V. (Srinivas V.), Grunin, M. (Michelle), Hagbi-Levi, S. (Shira), Campochiaro, B. (Betsy), Katsanis, N. (Nicholas), Holz, F.G. (Frank), Blond, F. (Frédéric), Blanché, H. (Hél'ne), Deleuze, J.-F. (Jean-Fran'ois), Igo Jr., R.P. (Robert), Truitt, B.J. (Barbara), Peachey, N.S. (Neal ), Meuer, S.M. (Stacy), Myers, C.E. (Chelsea), Moore, E.L. (Emily L.), Klein, R. (Ronald), Hauser, M.A. (Michael), Postel, E.A. (Eric), Courtenay, M.D. (Monique D.), Schwartz, S.M. (Stephen), Kovach, J.L. (Jaclyn), Scott, W.K. (William), Liew, G. (Gerald), Tan, A.G. (Ava G.), Gopinath, B. (Bamini), Smith, T. (Tim), Khan, J.C. (Jane), Shahid, M. (Mohammad), Moore, A.T. (Anthony), McGrath, J.A. (J Allie), Laux, R. (Reneé), Brantley, M.A. (Milam), Agarwal, A. (Anita), Ersoy, L. (Lebriz), Caramoy, A. (Albert), Langmann, T. (Thomas), Saksens, N.T.M. (Nicole T.), Jong, E.K. (Eiko Kde), Hoyng, C.B. (Carel), Cain, M.S. (Melinda), Richardson, A.J. (Andrea), Martin, T.M. (Tammy M.), Blangero, J. (John), Weeks, D.E. (Daniel), Dhillon, B. (Bal), Duijn, C.M. (Cornelia) van, Doheny, K.F. (Kimberly), Romm, J. (Jane), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Gorin, M.B. (Michael B.), Klein, M.L. (Michael), Baird, P.N. (Paul), Hollander, A.I. (Anneke), Fauser, S. (Sascha), WYates, J.R. (John R.), Allikmets, R. (Rando), Wang, J.J. (Jie Jin), Schaumberg, D.A. (Debra), Klein, B.E.K. (Barbara), Hagstrom, S.A. (Stephanie), Chowers, Y. (Yehuda), Lotery, A.J. (Andrew), Léveillard, T. (Thierry), Zhang, K. (Kang), Brilliant, M.H. (Murray H.), Hewit, A.W. (Alex), Swaroop, A. (Anand), Chew, E.Y. (Emily Y.), Pericak-Vance, M.A. (Margaret), DeAngelis, M.M. (Margaret), Stambolian, D. (Dwight), Haines, J.L. (Jonathan), Iyengar, S.K. (Sudha), Weber, B.H.F. (Bernhard), Abecasis, G.R. (Gonçalo), Heid, I.M. (Iris), and Li, M. (Mingyao)
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10 -8) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10 -10). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Published: 2016
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30. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016
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31. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author: Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
Published: 2016
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32. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, Makela, KM, Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, and Makela, KM
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016

33. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Author: Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, Heid, IM, Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, and Heid, IM
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Published: 2016

34. A novel, autosomal-recessive form of cardioskeletal myopathy and neutropenia with iron deficiency and Parkinsonism

Author: Brooks, D.G., Lech, G., VandenBorne, K., Wilson, R.B., Stambolian, D., Chance, B., and Kelley, R.I.
Subjects: Genetic disorders -- Research, Gene mutations -- Research, Biological sciences
Published: 2001

35. L Ferritin Forms Crystalline Cataracts in Hyperferritinemia Cataract Syndrome

Author: Brooks, D.G., Manova-Todorova, K., and Stambolian, D.
Subjects: Genetic research -- Analysis, Human genetics -- Research, Cataract -- Genetic aspects, Eye diseases -- Genetic aspects, Biological sciences
Published: 2000

36. A mouse model of galactose-induced cataracts

Author: Huang, K., Ai, Y., Zheng, Z., O'Brien-Jenkins, A., Ning, C., Reynolds, R., Segal, S., Bernard, D.J., Winshaw-Boris, A., and Stambolian, D.
Subjects: Genetic research -- Analysis, Human genetics -- Research, Cataract -- Genetic aspects, Biological sciences
Published: 2000

37. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Author: Simpson, C.L., Wojciechowski, Robert, Polašek, Ozren, Benčić, Goran, and Stambolian, D.
Subjects: genetic structures, gene, SNP, genetics, eye diseases
Abstract: Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.
Published: 2014

38. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

Author: Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, VJM, Ikram, MK, Hoehn, R, Vitart, V, Hewitt, AW, Oexle, K, Makela, K-M, MacGregor, S, Pirastu, M, Fan, Q, Cheng, C-Y, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polasek, O, Campbell, H, Bencic, G, Wright, AF, Wedenoja, J, Zeller, T, Schillert, A, Mirshahi, A, Lackner, K, Yip, SP, Yap, MKH, Ried, JS, Gieger, C, Murgia, F, Wilson, JF, Fleck, B, Yazar, S, Vingerling, JR, Hofman, A, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, BA, Zhou, X, Teo, Y-Y, Tai, ES, Vithana, E, Barathi, V, Zheng, Y, Siantar, RG, Neelam, K, Shin, Y, Lam, J, Yonova-Doing, E, Venturini, C, Hosseini, SM, Wong, H-S, Lehtimaki, T, Kahonen, M, Raitakari, O, Timpson, NJ, Evans, DM, Khor, C-C, Aung, T, Young, TL, Mitchell, P, Klein, B, van Duijn, CM, Meitinger, T, Jonas, JB, Baird, PN, Mackey, DA, Wong, TY, Saw, S-M, Parssinen, O, Stambolian, D, Hammond, CJ, Klaver, CCW, Williams, C, Paterson, AD, Bailey-Wilson, JE, Guggenheim, JA, Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, VJM, Ikram, MK, Hoehn, R, Vitart, V, Hewitt, AW, Oexle, K, Makela, K-M, MacGregor, S, Pirastu, M, Fan, Q, Cheng, C-Y, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polasek, O, Campbell, H, Bencic, G, Wright, AF, Wedenoja, J, Zeller, T, Schillert, A, Mirshahi, A, Lackner, K, Yip, SP, Yap, MKH, Ried, JS, Gieger, C, Murgia, F, Wilson, JF, Fleck, B, Yazar, S, Vingerling, JR, Hofman, A, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, BA, Zhou, X, Teo, Y-Y, Tai, ES, Vithana, E, Barathi, V, Zheng, Y, Siantar, RG, Neelam, K, Shin, Y, Lam, J, Yonova-Doing, E, Venturini, C, Hosseini, SM, Wong, H-S, Lehtimaki, T, Kahonen, M, Raitakari, O, Timpson, NJ, Evans, DM, Khor, C-C, Aung, T, Young, TL, Mitchell, P, Klein, B, van Duijn, CM, Meitinger, T, Jonas, JB, Baird, PN, Mackey, DA, Wong, TY, Saw, S-M, Parssinen, O, Stambolian, D, Hammond, CJ, Klaver, CCW, Williams, C, Paterson, AD, Bailey-Wilson, JE, and Guggenheim, JA
Abstract: 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.
Published: 2015

39. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia (vol 45, pg 314, 2013)

Author: Verhoeven, Virginie, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Hohn, R, Macgregor, S, Hewitt, AW, Nag, A, Cheng, CY (Ching-Yu), Yonova-Doing, E, Zhou, X, Ikram, Kamran, Buitendijk, Gabriëlle, McMahon, G, Kemp, JP, St Pourcain, B, Simpson, CL, Makela, KM, Lehtimaki, T, Kahonen, M, Paterson, AD, Hosseini, SM, Wong, HS, Xu, L, Jonas, JB, Parssinen, O, Wedenoja, J, Yip, SP, Ho, DWH, Pang, CP, Chen, LJ, Burdon, KP, Craig, JE, Klein, BEK, Klein, R, Haller, T, Metspalu, A, Khor, CC, Tai, ES, Aung, T, Vithana, E, Tay, WT, Barathi, VA, Chen, Peng, Li, RY, Liao, JM, Zheng, YF, Ong, RT, Doring, A, Evans, DM, Timpson, NJ, Verkerk, AJMH, Meitinger, T, Raitakari, O, Hawthorne, F, Spector, TD, Karssen, Lennart, Pirastu, M, Murgia, F, Ang, W, Mishra, A, Montgomery, GW, Pennell, CE, Cumberland, PM, Cotlarciuc, I, Mitchell, P, Wang, JJ, Schache, M, Janmahasathian, S, Igo, RP, Lass, JH, Chew, E, KIyengar, S, Gorgels, TGMF (Theo), Rudan, I, Hayward, C, Wright, AF, Polasek, O, Vatavuk, Z, Wilson, JF, Fleck, B, Zeller, T, Mirshahi, A, Müller, Caspar, Uitterlinden, André, Rivadeneira, Fernando, Vingerling, Hans, Hofman, Bert, Oostra, Ben, Amin, Najaf, Bergen, Arthur, Teo, YY, Rahi, JS, Vitart, V, Williams, C, Baird, PN, Wong, TY (Tien Yin), Oexle, K, Pfeiffer, N, Mackey, DA, Young, TL, Duijn, Cornelia, Saw, SM, Bailey-Wilson, JE, Stambolian, D, Klaver, Caroline, Hammond, CJ, Ophthalmology, Pathology, Epidemiology, Cell biology, Anesthesiology, Internal Medicine, Clinical Genetics, and Obstetrics & Gynecology
Published: 2013

40. Global Burden of Visual Impairment and Blindness

Author: Bourne, R, Price, H, Stevens, G, Tielsch, J, Wong, T, Brown, D, Chakravarthy, U, Ellwein, L, Jonas, J, Keeffe, J, Kuper, H, Leasher, J, Maguire, M, Musch, D, Naidoo, K, Parodi, M, Sieving, P, Taylor, H, Frick, K, Pesudovs, K, Friedman, D, Dandona, R, Dandona, L, Volmink, J, Robin, A, Javitt, J, Resnikoff, S, Gichuhi, S, Kymes, S, Limburg, H, Virgili, G, Pena, Fy, Sandar, M, Lanzetta, Paolo, Kim, J, Lambrou, G, Stambolian, D, Wiedemann, P, Arditi, A, Barkana, Y, Bozkurt, B, Budenz, D, Cai, F, Choi, J, Dekaris, I, Deva, J, Dreer, L, Frazier, M, Gazzard, A, Hammond, B, Hartnett, Me, Hirai, F, Huang, J, Joslin, C, Lim, J, Morse, A, Raju, M, Rossetti, L, Serle, J, Shen, T, Shetty, R, Tejedor, J, Tsilimbaris, M, van Meurs, J, Palaiou, M, Ingram, A, Gao, H, Khairallah, M, Hejtmancik, J, Dana, R, Gonzalez, V, Bennett, M, Hiratsuka, Y, Kuhn, F, Van, L, Sitorus, Rs, Wormald, R, and Del Monte, D.
Published: 2012

41. Erratum: Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population

Author: Diniz, B, primary, Rodger, D C, additional, Chavali, V R, additional, MacKay, T, additional, Lee, S Y, additional, Stambolian, D, additional, and Sadda, S V R, additional
Published: 2015
Full Text: View/download PDF

42. Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

Author: Miao, X, Simpson, CL, Wojciechowski, R, Oexle, K, Murgia, F, Portas, L, Li, X, Verhoeven, VJM, Vitart, V, Schache, M, Hosseini, SM, Hysi, PG, Raffel, LJ, Cotch, MF, Chew, E, Klein, BEK, Klein, R, Wong, TY, Van Duijn, CM, Mitchell, P, Saw, SM, Fossarello, M, Wang, JJ, Polasek, O, Campbell, H, Rudan, I, Oostra, BA, Uitterlinden, AG, Hofman, A, Rivadeneira, F, Amin, N, Karssen, LC, Vingerling, JR, Doering, A, Bettecken, T, Bencic, G, Gieger, C, Wichmann, H-E, Wilson, JF, Venturini, C, Fleck, B, Cumberland, PM, Rahi, JS, Hammond, CJ, Hayward, C, Wright, AF, Paterson, AD, Baird, PN, Klaver, CCW, Rotter, JI, Pirastu, M, Meitinger, T, Bailey-Wilson, JE, Stambolian, D, Miao, X, Simpson, CL, Wojciechowski, R, Oexle, K, Murgia, F, Portas, L, Li, X, Verhoeven, VJM, Vitart, V, Schache, M, Hosseini, SM, Hysi, PG, Raffel, LJ, Cotch, MF, Chew, E, Klein, BEK, Klein, R, Wong, TY, Van Duijn, CM, Mitchell, P, Saw, SM, Fossarello, M, Wang, JJ, Polasek, O, Campbell, H, Rudan, I, Oostra, BA, Uitterlinden, AG, Hofman, A, Rivadeneira, F, Amin, N, Karssen, LC, Vingerling, JR, Doering, A, Bettecken, T, Bencic, G, Gieger, C, Wichmann, H-E, Wilson, JF, Venturini, C, Fleck, B, Cumberland, PM, Rahi, JS, Hammond, CJ, Hayward, C, Wright, AF, Paterson, AD, Baird, PN, Klaver, CCW, Rotter, JI, Pirastu, M, Meitinger, T, Bailey-Wilson, JE, and Stambolian, D
Abstract: Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error acros
Published: 2014

43. Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

Author: Simpson, CL, Wojciechowski, R, Oexle, K, Murgia, F, Portas, L, Li, XH, Verhoeven, Virginie, Vitart, V, Schache, M, Hosseini, SM, Hysi, PG, Raffel, LJ, Cotch, MF, Chew, E, Klein, BEK, Klein, R, Wong, TY (Tien Yin), Duijn, Cornelia, Mitchell, P, Saw, SM, Fossarello, M, Wang, JJ, Polasek, O, Campbell, H, Rudan, I, Oostra, Ben, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Amin, Najaf, Karssen, Lennart, Vingerling, Hans, Doering, A, Bettecken, T, Bencic, G, Gieger, C, Wichmann, HE, Wilson, JF, Venturini, C, Fleck, B, Cumberland, PM, Rahi, JS, Hammond, CJ, Hayward, C, Wright, AF, Paterson, AD, Baird, PN, Klaver, Caroline, Rotter, JI, Pirastu, M, Meitinger, T, Bailey-Wilson, JE, Stambolian, D, Simpson, CL, Wojciechowski, R, Oexle, K, Murgia, F, Portas, L, Li, XH, Verhoeven, Virginie, Vitart, V, Schache, M, Hosseini, SM, Hysi, PG, Raffel, LJ, Cotch, MF, Chew, E, Klein, BEK, Klein, R, Wong, TY (Tien Yin), Duijn, Cornelia, Mitchell, P, Saw, SM, Fossarello, M, Wang, JJ, Polasek, O, Campbell, H, Rudan, I, Oostra, Ben, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Amin, Najaf, Karssen, Lennart, Vingerling, Hans, Doering, A, Bettecken, T, Bencic, G, Gieger, C, Wichmann, HE, Wilson, JF, Venturini, C, Fleck, B, Cumberland, PM, Rahi, JS, Hammond, CJ, Hayward, C, Wright, AF, Paterson, AD, Baird, PN, Klaver, Caroline, Rotter, JI, Pirastu, M, Meitinger, T, Bailey-Wilson, JE, and Stambolian, D
Abstract: Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25x10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11x10(-11)) and 8q12 (minimum p value 1.82x10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage-disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level'' association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error acros
Published: 2014

44. Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population

Author: Diniz, B, primary, Rodger, D C, additional, Chavali, V R, additional, MacKay, T, additional, Lee, S Y, additional, Stambolian, D, additional, and Sadda, S V R, additional
Published: 2014
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45. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration

Author: Zhan, X, Larson, DE, Wang, C, Koboldt, DC, Sergeev, YV, Fulton, RS, Fulton, LL, Fronick, CC, Branham, KE, Bragg-Gresham, J, Jun, G, Hu, Y, Kang, HM, Liu, D, Othman, M, Brooks, M, Ratnapriya, R, Boleda, A, Grassmann, F, von Strachwitz, C, Olson, LM, Buitendijk, GHS, Hofman, A, van Duijn, CM, Cipriani, V, Moore, AT, Shahid, H, Jiang, Y, Conley, YP, Morgan, DJ, Kim, IK, Johnson, MP, Cantsilieris, S, Richardson, AJ, Guymer, RH, Luo, H, Ouyang, H, Licht, C, Pluthero, FG, Zhang, MM, Zhang, K, Baird, PN, Blangero, J, Klein, ML, Farrer, LA, DeAngelis, MM, Weeks, DE, Gorin, MB, Yates, JRW, Klaver, CCW, Pericak-Vance, MA, Haines, JL, Weber, BHF, Wilson, RK, Heckenlively, JR, Chew, EY, Stambolian, D, Mardis, ER, Swaroop, A, Abecasis, GR, Zhan, X, Larson, DE, Wang, C, Koboldt, DC, Sergeev, YV, Fulton, RS, Fulton, LL, Fronick, CC, Branham, KE, Bragg-Gresham, J, Jun, G, Hu, Y, Kang, HM, Liu, D, Othman, M, Brooks, M, Ratnapriya, R, Boleda, A, Grassmann, F, von Strachwitz, C, Olson, LM, Buitendijk, GHS, Hofman, A, van Duijn, CM, Cipriani, V, Moore, AT, Shahid, H, Jiang, Y, Conley, YP, Morgan, DJ, Kim, IK, Johnson, MP, Cantsilieris, S, Richardson, AJ, Guymer, RH, Luo, H, Ouyang, H, Licht, C, Pluthero, FG, Zhang, MM, Zhang, K, Baird, PN, Blangero, J, Klein, ML, Farrer, LA, DeAngelis, MM, Weeks, DE, Gorin, MB, Yates, JRW, Klaver, CCW, Pericak-Vance, MA, Haines, JL, Weber, BHF, Wilson, RK, Heckenlively, JR, Chew, EY, Stambolian, D, Mardis, ER, Swaroop, A, and Abecasis, GR
Abstract: Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p.Arg1210Cys encoded in the CFH gene (case frequency (fcase) = 0.51%; control frequency (fcontrol) = 0.02%; odds ratio (OR) = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (fcase = 1.06%; fcontrol = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.
Published: 2013

46. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Author: Verhoeven, VJM, Hysi, PG, Saw, S-M, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, MK, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, C-C, Fan, Q, Zhou, X, Young, TL, Tai, E-S, Goh, L-K, Li, Y-J, Aung, T, Vithana, E, Teo, Y-Y, Tay, W, Sim, X, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Campbell, H, Wilson, JF, Fleck, BW, Nakata, I, Yoshimura, N, Yamada, R, Matsuda, F, Ohno-Matsui, K, Nag, A, McMahon, G, St Pourcain, B, Lu, Y, Rahi, JS, Cumberland, PM, Bhattacharya, S, Simpson, CL, Atwood, LD, Li, X, Raffel, LJ, Murgia, F, Portas, L, Despriet, DDG, van Koolwijk, LME, Wolfram, C, Lackner, KJ, Toenjes, A, Maegi, R, Lehtimaki, T, Kahonen, M, Esko, T, Metspalu, A, Rantanen, T, Parssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, BA, Smith, AV, de Jong, PTVM, Hofman, A, Amin, N, Karssen, LC, Rivadeneira, F, Vingerling, JR, Eiriksdottir, G, Gudnason, V, Doering, A, Bettecken, T, Uitterlinden, AG, Williams, C, Zeller, T, Castagne, R, Oexle, K, van Duijn, CM, Iyengar, SK, Mitchell, P, Wang, JJ, Hoehn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, T-Y, Hammond, CJ, Klaver, CCW, Verhoeven, VJM, Hysi, PG, Saw, S-M, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, MK, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, C-C, Fan, Q, Zhou, X, Young, TL, Tai, E-S, Goh, L-K, Li, Y-J, Aung, T, Vithana, E, Teo, Y-Y, Tay, W, Sim, X, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Campbell, H, Wilson, JF, Fleck, BW, Nakata, I, Yoshimura, N, Yamada, R, Matsuda, F, Ohno-Matsui, K, Nag, A, McMahon, G, St Pourcain, B, Lu, Y, Rahi, JS, Cumberland, PM, Bhattacharya, S, Simpson, CL, Atwood, LD, Li, X, Raffel, LJ, Murgia, F, Portas, L, Despriet, DDG, van Koolwijk, LME, Wolfram, C, Lackner, KJ, Toenjes, A, Maegi, R, Lehtimaki, T, Kahonen, M, Esko, T, Metspalu, A, Rantanen, T, Parssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, BA, Smith, AV, de Jong, PTVM, Hofman, A, Amin, N, Karssen, LC, Rivadeneira, F, Vingerling, JR, Eiriksdottir, G, Gudnason, V, Doering, A, Bettecken, T, Uitterlinden, AG, Williams, C, Zeller, T, Castagne, R, Oexle, K, van Duijn, CM, Iyengar, SK, Mitchell, P, Wang, JJ, Hoehn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, T-Y, Hammond, CJ, and Klaver, CCW
Abstract: Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
Published: 2012

47. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Author: Verhoeven, Virginie, Hysi, PG, Saw, SM, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, Kamran, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, CC, Fan, Q, Zhou, X, Young, TL, Tai, ES, Goh, LK, Li, YJ, Aung, T, Vithana, E, Teo, YY, Tay, W, Sim, X, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Campbell, H, Wilson, JF, Fleck, BW, Nakata, I, Yoshimura, N, Yamada, R, Matsuda, F, Ohno-Matsui, K, Nag, A, McMahon, G, St Pourcain, B, Lu, Y (Yi), Rahi, JS, Cumberland, PM, Bhattacharya, S, Simpson, CL, Atwood, LD, Li, XH, Raffel, LJ, Murgia, F, Portas, L, Despriet, Dominiek, Koolwijk, Leonieke, Wolfram, C, Lackner, KJ, Tonjes, A, Magi, R, Lehtimaki, T, Kahonen, M, Esko, T, Metspalu, A, Rantanen, T, Parssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, Ben, Smith, AV, de Jong, PTVM (Paulus), Hofman, Bert, Amin, Najaf, Karssen, Lennart, Rivadeneira, Fernando, Vingerling, Hans, Eiriksdottir, G, Gudnason, V, Doring, A, Bettecken, T, Uitterlinden, André, Williams, C, Zeller, T, Castagne, R, Oexle, K, Duijn, Cornelia, Iyengar, SK, Mitchell, P, Wang, JJ, Hohn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, TY, Hammond, CJ, Klaver, Caroline, Verhoeven, Virginie, Hysi, PG, Saw, SM, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, Kamran, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, CC, Fan, Q, Zhou, X, Young, TL, Tai, ES, Goh, LK, Li, YJ, Aung, T, Vithana, E, Teo, YY, Tay, W, Sim, X, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Campbell, H, Wilson, JF, Fleck, BW, Nakata, I, Yoshimura, N, Yamada, R, Matsuda, F, Ohno-Matsui, K, Nag, A, McMahon, G, St Pourcain, B, Lu, Y (Yi), Rahi, JS, Cumberland, PM, Bhattacharya, S, Simpson, CL, Atwood, LD, Li, XH, Raffel, LJ, Murgia, F, Portas, L, Despriet, Dominiek, Koolwijk, Leonieke, Wolfram, C, Lackner, KJ, Tonjes, A, Magi, R, Lehtimaki, T, Kahonen, M, Esko, T, Metspalu, A, Rantanen, T, Parssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, Ben, Smith, AV, de Jong, PTVM (Paulus), Hofman, Bert, Amin, Najaf, Karssen, Lennart, Rivadeneira, Fernando, Vingerling, Hans, Eiriksdottir, G, Gudnason, V, Doring, A, Bettecken, T, Uitterlinden, André, Williams, C, Zeller, T, Castagne, R, Oexle, K, Duijn, Cornelia, Iyengar, SK, Mitchell, P, Wang, JJ, Hohn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, TY, Hammond, CJ, and Klaver, Caroline
Abstract: Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
Published: 2012

48. Complement factor d in age-related macular degeneration

Author: Stanton, C.M., Yates, J.R.W., Hollander, A.I. den, Seddon, J.M., Swaroop, A., Stambolian, D., Fauser, S., Hoyng, C.B., Yu, Y., Atsuhiro, K., Branham, K., Othman, M., Chen, W., Kortvely, E., Chalmers, K., Hayward, C., Moore, A.T., Dhillon, B., Ueffing, M., Wright, A.F., Stanton, C.M., Yates, J.R.W., Hollander, A.I. den, Seddon, J.M., Swaroop, A., Stambolian, D., Fauser, S., Hoyng, C.B., Yu, Y., Atsuhiro, K., Branham, K., Othman, M., Chen, W., Kortvely, E., Chalmers, K., Hayward, C., Moore, A.T., Dhillon, B., Ueffing, M., and Wright, A.F.
Abstract: Contains fulltext : 96746.pdf (publisher's version ) (Closed access), Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis.
Published: 2011

49. Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies.

Author: McKay, G.J., Patterson, C.C., Chakravarthy, U., Dasari, S., Klaver, C.C., Vingerling, J.R., Ho, L., de Jong, P.T.V.M., Fletcher, A.E., Young, I.S., Seland, J.H., Rahhu, M., Soubrane, G., Tomazzoli, L., Topouzis, F., Vioque, J., Hingorani, A.D., Sofat, R., Dean, M., Sawitzke, J., Seddon, J.M., Peter, I., Webster, A.R., Moore, A.T., Yates, J.R., Cipriani, V., Fritsche, L.G., Weber, B.H., Keilhauer, C.N., Lotery, A.J., Ennis, S., Klein, M.L., Francis, P.J., Stambolian, D., Orlin, A., Gorin, M.B., Weeks, D.E., Kuo, C.L., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G.R., Wright, A.F., Hayward, C., Baird, P.N., Guymer, R.H., Attia, J., Thakkinstian, A., Silvestri, G., McKay, G.J., Patterson, C.C., Chakravarthy, U., Dasari, S., Klaver, C.C., Vingerling, J.R., Ho, L., de Jong, P.T.V.M., Fletcher, A.E., Young, I.S., Seland, J.H., Rahhu, M., Soubrane, G., Tomazzoli, L., Topouzis, F., Vioque, J., Hingorani, A.D., Sofat, R., Dean, M., Sawitzke, J., Seddon, J.M., Peter, I., Webster, A.R., Moore, A.T., Yates, J.R., Cipriani, V., Fritsche, L.G., Weber, B.H., Keilhauer, C.N., Lotery, A.J., Ennis, S., Klein, M.L., Francis, P.J., Stambolian, D., Orlin, A., Gorin, M.B., Weeks, D.E., Kuo, C.L., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G.R., Wright, A.F., Hayward, C., Baird, P.N., Guymer, R.H., Attia, J., Thakkinstian, A., and Silvestri, G.
Published: 2011

50. Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people.

Author: McKay, G.J., Silvestri, G., Chakravarthy, U., Dasari, S., Fritsche, L.G., Weber, B.H., Keilhauer, C.N., Klein, M.L., Francis, P.J., Klaver, C.C., Vingerling, J.R., Ho, L., de Jong, P.T.V.M., Dean, M., Sawitzke, J., Baird, P.N., Guymer, R.H., Stambolian, D., Orlin, A., Seddon, J.M., Peter, I., Wright, A.F., Hayward, C., Lotery, A.J., Ennis, S., Gorin, M.B., Weeks, D.E., Kuo, C.L., Hingorani, A.D., Sofat, R., Cipriani, V., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G.R., Yates, J.R., Webster, A.R., Moore, A.T., Seland, J.H., Rahu, M., Soubrane, G., Tomazolli, L., Topouzis, F., Vioque, J., Young, I.S., Fletcher, A.E., Patterson, C.C., McKay, G.J., Silvestri, G., Chakravarthy, U., Dasari, S., Fritsche, L.G., Weber, B.H., Keilhauer, C.N., Klein, M.L., Francis, P.J., Klaver, C.C., Vingerling, J.R., Ho, L., de Jong, P.T.V.M., Dean, M., Sawitzke, J., Baird, P.N., Guymer, R.H., Stambolian, D., Orlin, A., Seddon, J.M., Peter, I., Wright, A.F., Hayward, C., Lotery, A.J., Ennis, S., Gorin, M.B., Weeks, D.E., Kuo, C.L., Hingorani, A.D., Sofat, R., Cipriani, V., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G.R., Yates, J.R., Webster, A.R., Moore, A.T., Seland, J.H., Rahu, M., Soubrane, G., Tomazolli, L., Topouzis, F., Vioque, J., Young, I.S., Fletcher, A.E., and Patterson, C.C.
Published: 2011

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