IMI - Myopia Genetics Report

CREAM Consortium

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)M89-M105
Number of pages17
JournalInvestigative ophthalmology & visual science
Volume60
Issue number3
DOIs
Publication statusPublished - Feb 2019

Cite this

CREAM Consortium. / IMI - Myopia Genetics Report. In: Investigative ophthalmology & visual science. 2019 ; Vol. 60, No. 3. pp. M89-M105.
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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.",
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author = "{CREAM Consortium} and Tedja, {Milly S.} and Haarman, {Annechien E. G.} and Meester-Smoor, {Magda A.} and Jaakko Kaprio and Mackey, {David A.} and Guggenheim, {Jeremy A.} and Hammond, {Christopher J.} and Verhoeven, {Virginie J. M.} and Klaver, {Caroline C. W.} and Bailey-Wilson, {Joan E.} and Baird, {Paul Nigel} and Veluchamy, {Amutha Barathi} and Ginevra Biino and Burdon, {Kathryn P.} and Harry Campbell and Chen, {Li Jia} and Ching-Yu Cheng and Chew, {Emily Y.} and Craig, {Jamie E.} and Cumberland, {Phillippa M.} and Deangelis, {Margaret M.} and Cecile Delcourt and Xiaohu Ding and {van Duijn}, {Cornelia M.} and Evans, {David M.} and Qiao Fan and Maurizio Fossarello and Foster, {Paul J.} and Puya Gharahkhani and Iglesias, {Adriana I.} and Xiaobo Guol and Toomas Haller and Xikun Han and Caroline Hayward and Mingguang He and Hewitt, {Alex W.} and Quan Hoang and Hysi, {Pirro G.} and Igo, {Robert P.} and Iyengar, {Sudha K.} and Jonas, {Jost B.} and Mika Kahonen and Khawaja, {Anthony P.} and Klein, {Barbara E.} and Ronald Klein and Lass, {Jonathan H.} and Kris Lee and Terho Lehtimaki and Deyana Lewis and Qing Li and Shi-Ming Li and Leo-Pekka Lyytikainen and Stuart MacGregor and Martin, {Nicholas G.} and Akira Meguro and Andres Metspalu and Candace Middlebrooks and Masahiro Miyake and Nobuhisa Mizuki and Anthony Musolf and Stefan Nickels and Konrad Oexle and Pang, {Chi Pui} and Olavi Parssinen and Paterson, {Andrew D.} and Norbert Pfeiffer and Ozren Polasek and Rahi, {Jugnoo S.} and Olli Raitakari and Igor Rudan and Srujana Sahebjada and Seang-Mei Saw and Dwight Stambolian and Simpson, {Claire L.} and E-Shyong Tai and Tideman, {J. Willem L.} and Akitaka Tsujikawa and Verhoeven, {Virginie J. M.} and Veronique Vitart and Ningli Wang and Juho Wedenoja and Wei, {Wen Bin} and Cathy Williams and Williams, {Katie M.} and Wilson, {James F.} and Robert Wojciechowski and Wang, {Ya Xing} and Kenji Yamashiro and Yam, {Jason C. S.} and Yap, {Maurice K. H.} and Seyhan Yazar and Yip, {Shea Ping} and Young, {Terri L.} and Xiangtian Zhou",
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IMI - Myopia Genetics Report. / CREAM Consortium.

In: Investigative ophthalmology & visual science, Vol. 60, No. 3, 02.2019, p. M89-M105.

Research output: Contribution to journalArticle

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

VL - 60

SP - M89-M105

JO - Investigative Ophthalmology & Visual Science (IOVS)

JF - Investigative Ophthalmology & Visual Science (IOVS)

SN - 0146-0404

IS - 3

ER -