TY - JOUR
T1 - IMI - Myopia Genetics Report
AU - CREAM Consortium
AU - Tedja, Milly S.
AU - Haarman, Annechien E. G.
AU - Meester-Smoor, Magda A.
AU - Kaprio, Jaakko
AU - Mackey, David A.
AU - Guggenheim, Jeremy A.
AU - Hammond, Christopher J.
AU - Verhoeven, Virginie J. M.
AU - Klaver, Caroline C. W.
AU - Bailey-Wilson, Joan E.
AU - Baird, Paul Nigel
AU - Veluchamy, Amutha Barathi
AU - Biino, Ginevra
AU - Burdon, Kathryn P.
AU - Campbell, Harry
AU - Chen, Li Jia
AU - Cheng, Ching-Yu
AU - Chew, Emily Y.
AU - Craig, Jamie E.
AU - Cumberland, Phillippa M.
AU - Deangelis, Margaret M.
AU - Delcourt, Cecile
AU - Ding, Xiaohu
AU - van Duijn, Cornelia M.
AU - Evans, David M.
AU - Fan, Qiao
AU - Fossarello, Maurizio
AU - Foster, Paul J.
AU - Gharahkhani, Puya
AU - Iglesias, Adriana I.
AU - Guol, Xiaobo
AU - Haller, Toomas
AU - Han, Xikun
AU - Hayward, Caroline
AU - He, Mingguang
AU - Hewitt, Alex W.
AU - Hoang, Quan
AU - Hysi, Pirro G.
AU - Igo, Robert P.
AU - Iyengar, Sudha K.
AU - Jonas, Jost B.
AU - Kahonen, Mika
AU - Khawaja, Anthony P.
AU - Klein, Barbara E.
AU - Klein, Ronald
AU - Lass, Jonathan H.
AU - Lee, Kris
AU - Lehtimaki, Terho
AU - Lewis, Deyana
AU - Li, Qing
AU - Li, Shi-Ming
AU - Lyytikainen, Leo-Pekka
AU - MacGregor, Stuart
AU - Martin, Nicholas G.
AU - Meguro, Akira
AU - Metspalu, Andres
AU - Middlebrooks, Candace
AU - Miyake, Masahiro
AU - Mizuki, Nobuhisa
AU - Musolf, Anthony
AU - Nickels, Stefan
AU - Oexle, Konrad
AU - Pang, Chi Pui
AU - Parssinen, Olavi
AU - Paterson, Andrew D.
AU - Pfeiffer, Norbert
AU - Polasek, Ozren
AU - Rahi, Jugnoo S.
AU - Raitakari, Olli
AU - Rudan, Igor
AU - Sahebjada, Srujana
AU - Saw, Seang-Mei
AU - Stambolian, Dwight
AU - Simpson, Claire L.
AU - Tai, E-Shyong
AU - Tideman, J. Willem L.
AU - Tsujikawa, Akitaka
AU - Verhoeven, Virginie J. M.
AU - Vitart, Veronique
AU - Wang, Ningli
AU - Wedenoja, Juho
AU - Wei, Wen Bin
AU - Williams, Cathy
AU - Williams, Katie M.
AU - Wilson, James F.
AU - Wojciechowski, Robert
AU - Wang, Ya Xing
AU - Yamashiro, Kenji
AU - Yam, Jason C. S.
AU - Yap, Maurice K. H.
AU - Yazar, Seyhan
AU - Yip, Shea Ping
AU - Young, Terri L.
AU - Zhou, Xiangtian
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - myopia
KW - refractive error
KW - genetics
KW - GWAS
KW - GxE interactions
KW - GENOME-WIDE ASSOCIATION
KW - HEPATOCYTE GROWTH-FACTOR
KW - HIGH-GRADE MYOPIA
KW - ONSET HIGH MYOPIA
KW - REFRACTIVE ERROR
KW - SUSCEPTIBILITY LOCUS
KW - CORNEAL CURVATURE
KW - AXIAL LENGTH
KW - PAX6 GENE
KW - MENDELIAN RANDOMIZATION
U2 - 10.1167/iovs.18-25965
DO - 10.1167/iovs.18-25965
M3 - Article
C2 - 30817828
SN - 0146-0404
VL - 60
SP - M89-M105
JO - Investigative ophthalmology & visual science
JF - Investigative ophthalmology & visual science
IS - 3
ER -