Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Virginie J.M. Verhoeven, Pirro G. Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A. Guggenheim, René Höhn, Stuart Macgregor, Alex W. Hewitt, Abhishek Nag, Ching Yu Cheng, Ekaterina Yonova-Doing, Xin Zhou, M. Kamran Ikram, Gabriëlle H.S. Buitendijk, George Mcmahon, John P. Kemp, Beate St Pourcain, Claire Simpson, Kari Matti Mäkelä, Terho LehtimäkiMika Kähönen, Andrew D. Paterson, S. Mohsen Hosseini, Hoi Suen Wong, Liang Xu, Jost B. Jonas, Olavi Pärssinen, Juho Wedenoja, Shea Ping Yip, Daniel W.H. Ho, Chi Pui Pang, Li Jia Chen, Kathryn P. Burdon, Jamie E. Craig, Barbara E.K. Klein, Ronald Klein, Toomas Haller, Andres Metspalu, Chiea Chuen Khor, E. Shyong Tai, Tin Aung, Eranga Vithana, Wan Ting Tay, Veluchamy A. Barathi, Peng Chen, Ruoying Li, Jiemin Liao, Yingfeng Zheng, Rick T. Ong, Angela Döring, David M. Evans, Nicholas J. Timpson, Annemieke J.M.H. Verkerk, Thomas Meitinger, Olli Raitakari, Felicia Hawthorne, Tim D. Spector, Lennart C. Karssen, Mario Pirastu, Federico Murgia, Wei Ang, Aniket Mishra, Grant W. Montgomery, Craig E. Pennell, Phillippa M. Cumberland, Ioana Cotlarciuc, Paul Mitchell, Jie Jin Wang, Maria Schache, Sarayut Janmahasathian, Robert P. Igo, Jonathan H. Lass, Emily Chew, Sudha K. Iyengar, Theo G.M.F. Gorgels, Igor Rudan, Caroline Hayward, Alan F. Wright, Ozren Polasek, Zoran Vatavuk, James F. Wilson, Brian Fleck, Tanja Zeller, Alireza Mirshahi, Christian Müller, André G. Uitterlinden, Fernando Rivadeneira, Johannes R. Vingerling, Albert Hofman, Ben A. Oostra, Najaf Amin, Arthur A.B. Bergen, Yik Ying Teo, Jugnoo S. Rahi, Veronique Vitart, Cathy Williams, Paul N. Baird, Tien Yin Wong, Konrad Oexle, Norbert Pfeiffer, David A. Mackey, Terri L. Young, Cornelia M. Van Duijn, Seang Mei Saw, Joan E. Bailey-Wilson, Dwight Stambolian, Caroline C. Klaver, Christopher J. Hammond

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

Original languageEnglish (US)
Pages (from-to)314-318
Number of pages5
JournalNature Genetics
Volume45
Issue number3
DOIs
StatePublished - Mar 1 2013

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Refractive Errors
Myopia
Meta-Analysis
Genome
Genetic Load
Ion Transport
Blindness
Tretinoin
Synaptic Transmission
Single Nucleotide Polymorphism
Extracellular Matrix
Population
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Verhoeven, V. J. M., Hysi, P. G., Wojciechowski, R., Fan, Q., Guggenheim, J. A., Höhn, R., ... Hammond, C. J. (2013). Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics, 45(3), 314-318. https://doi.org/10.1038/ng.2554

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. / Verhoeven, Virginie J.M.; Hysi, Pirro G.; Wojciechowski, Robert; Fan, Qiao; Guggenheim, Jeremy A.; Höhn, René; Macgregor, Stuart; Hewitt, Alex W.; Nag, Abhishek; Cheng, Ching Yu; Yonova-Doing, Ekaterina; Zhou, Xin; Ikram, M. Kamran; Buitendijk, Gabriëlle H.S.; Mcmahon, George; Kemp, John P.; Pourcain, Beate St; Simpson, Claire; Mäkelä, Kari Matti; Lehtimäki, Terho; Kähönen, Mika; Paterson, Andrew D.; Hosseini, S. Mohsen; Wong, Hoi Suen; Xu, Liang; Jonas, Jost B.; Pärssinen, Olavi; Wedenoja, Juho; Yip, Shea Ping; Ho, Daniel W.H.; Pang, Chi Pui; Chen, Li Jia; Burdon, Kathryn P.; Craig, Jamie E.; Klein, Barbara E.K.; Klein, Ronald; Haller, Toomas; Metspalu, Andres; Khor, Chiea Chuen; Tai, E. Shyong; Aung, Tin; Vithana, Eranga; Tay, Wan Ting; Barathi, Veluchamy A.; Chen, Peng; Li, Ruoying; Liao, Jiemin; Zheng, Yingfeng; Ong, Rick T.; Döring, Angela; Evans, David M.; Timpson, Nicholas J.; Verkerk, Annemieke J.M.H.; Meitinger, Thomas; Raitakari, Olli; Hawthorne, Felicia; Spector, Tim D.; Karssen, Lennart C.; Pirastu, Mario; Murgia, Federico; Ang, Wei; Mishra, Aniket; Montgomery, Grant W.; Pennell, Craig E.; Cumberland, Phillippa M.; Cotlarciuc, Ioana; Mitchell, Paul; Wang, Jie Jin; Schache, Maria; Janmahasathian, Sarayut; Igo, Robert P.; Lass, Jonathan H.; Chew, Emily; Iyengar, Sudha K.; Gorgels, Theo G.M.F.; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Vatavuk, Zoran; Wilson, James F.; Fleck, Brian; Zeller, Tanja; Mirshahi, Alireza; Müller, Christian; Uitterlinden, André G.; Rivadeneira, Fernando; Vingerling, Johannes R.; Hofman, Albert; Oostra, Ben A.; Amin, Najaf; Bergen, Arthur A.B.; Teo, Yik Ying; Rahi, Jugnoo S.; Vitart, Veronique; Williams, Cathy; Baird, Paul N.; Wong, Tien Yin; Oexle, Konrad; Pfeiffer, Norbert; Mackey, David A.; Young, Terri L.; Van Duijn, Cornelia M.; Saw, Seang Mei; Bailey-Wilson, Joan E.; Stambolian, Dwight; Klaver, Caroline C.; Hammond, Christopher J.

In: Nature Genetics, Vol. 45, No. 3, 01.03.2013, p. 314-318.

Research output: Contribution to journalArticle

Verhoeven, VJM, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Höhn, R, Macgregor, S, Hewitt, AW, Nag, A, Cheng, CY, Yonova-Doing, E, Zhou, X, Ikram, MK, Buitendijk, GHS, Mcmahon, G, Kemp, JP, Pourcain, BS, Simpson, C, Mäkelä, KM, Lehtimäki, T, Kähönen, M, Paterson, AD, Hosseini, SM, Wong, HS, Xu, L, Jonas, JB, Pärssinen, 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, P, Li, R, Liao, J, Zheng, Y, Ong, RT, Döring, A, Evans, DM, Timpson, NJ, Verkerk, AJMH, Meitinger, T, Raitakari, O, Hawthorne, F, Spector, TD, Karssen, LC, 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, Iyengar, SK, Gorgels, TGMF, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Vatavuk, Z, Wilson, JF, Fleck, B, Zeller, T, Mirshahi, A, Müller, C, Uitterlinden, AG, Rivadeneira, F, Vingerling, JR, Hofman, A, Oostra, BA, Amin, N, Bergen, AAB, Teo, YY, Rahi, JS, Vitart, V, Williams, C, Baird, PN, Wong, TY, Oexle, K, Pfeiffer, N, Mackey, DA, Young, TL, Van Duijn, CM, Saw, SM, Bailey-Wilson, JE, Stambolian, D, Klaver, CC & Hammond, CJ 2013, 'Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia', Nature Genetics, vol. 45, no. 3, pp. 314-318. https://doi.org/10.1038/ng.2554
Verhoeven, Virginie J.M. ; Hysi, Pirro G. ; Wojciechowski, Robert ; Fan, Qiao ; Guggenheim, Jeremy A. ; Höhn, René ; Macgregor, Stuart ; Hewitt, Alex W. ; Nag, Abhishek ; Cheng, Ching Yu ; Yonova-Doing, Ekaterina ; Zhou, Xin ; Ikram, M. Kamran ; Buitendijk, Gabriëlle H.S. ; Mcmahon, George ; Kemp, John P. ; Pourcain, Beate St ; Simpson, Claire ; Mäkelä, Kari Matti ; Lehtimäki, Terho ; Kähönen, Mika ; Paterson, Andrew D. ; Hosseini, S. Mohsen ; Wong, Hoi Suen ; Xu, Liang ; Jonas, Jost B. ; Pärssinen, Olavi ; Wedenoja, Juho ; Yip, Shea Ping ; Ho, Daniel W.H. ; Pang, Chi Pui ; Chen, Li Jia ; Burdon, Kathryn P. ; Craig, Jamie E. ; Klein, Barbara E.K. ; Klein, Ronald ; Haller, Toomas ; Metspalu, Andres ; Khor, Chiea Chuen ; Tai, E. Shyong ; Aung, Tin ; Vithana, Eranga ; Tay, Wan Ting ; Barathi, Veluchamy A. ; Chen, Peng ; Li, Ruoying ; Liao, Jiemin ; Zheng, Yingfeng ; Ong, Rick T. ; Döring, Angela ; Evans, David M. ; Timpson, Nicholas J. ; Verkerk, Annemieke J.M.H. ; Meitinger, Thomas ; Raitakari, Olli ; Hawthorne, Felicia ; Spector, Tim D. ; Karssen, Lennart C. ; Pirastu, Mario ; Murgia, Federico ; Ang, Wei ; Mishra, Aniket ; Montgomery, Grant W. ; Pennell, Craig E. ; Cumberland, Phillippa M. ; Cotlarciuc, Ioana ; Mitchell, Paul ; Wang, Jie Jin ; Schache, Maria ; Janmahasathian, Sarayut ; Igo, Robert P. ; Lass, Jonathan H. ; Chew, Emily ; Iyengar, Sudha K. ; Gorgels, Theo G.M.F. ; Rudan, Igor ; Hayward, Caroline ; Wright, Alan F. ; Polasek, Ozren ; Vatavuk, Zoran ; Wilson, James F. ; Fleck, Brian ; Zeller, Tanja ; Mirshahi, Alireza ; Müller, Christian ; Uitterlinden, André G. ; Rivadeneira, Fernando ; Vingerling, Johannes R. ; Hofman, Albert ; Oostra, Ben A. ; Amin, Najaf ; Bergen, Arthur A.B. ; Teo, Yik Ying ; Rahi, Jugnoo S. ; Vitart, Veronique ; Williams, Cathy ; Baird, Paul N. ; Wong, Tien Yin ; Oexle, Konrad ; Pfeiffer, Norbert ; Mackey, David A. ; Young, Terri L. ; Van Duijn, Cornelia M. ; Saw, Seang Mei ; Bailey-Wilson, Joan E. ; Stambolian, Dwight ; Klaver, Caroline C. ; Hammond, Christopher J. / Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. In: Nature Genetics. 2013 ; Vol. 45, No. 3. pp. 314-318.
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T1 - Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

AU - Verhoeven, Virginie J.M.

AU - Hysi, Pirro G.

AU - Wojciechowski, Robert

AU - Fan, Qiao

AU - Guggenheim, Jeremy A.

AU - Höhn, René

AU - Macgregor, Stuart

AU - Hewitt, Alex W.

AU - Nag, Abhishek

AU - Cheng, Ching Yu

AU - Yonova-Doing, Ekaterina

AU - Zhou, Xin

AU - Ikram, M. Kamran

AU - Buitendijk, Gabriëlle H.S.

AU - Mcmahon, George

AU - Kemp, John P.

AU - Pourcain, Beate St

AU - Simpson, Claire

AU - Mäkelä, Kari Matti

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Paterson, Andrew D.

AU - Hosseini, S. Mohsen

AU - Wong, Hoi Suen

AU - Xu, Liang

AU - Jonas, Jost B.

AU - Pärssinen, Olavi

AU - Wedenoja, Juho

AU - Yip, Shea Ping

AU - Ho, Daniel W.H.

AU - Pang, Chi Pui

AU - Chen, Li Jia

AU - Burdon, Kathryn P.

AU - Craig, Jamie E.

AU - Klein, Barbara E.K.

AU - Klein, Ronald

AU - Haller, Toomas

AU - Metspalu, Andres

AU - Khor, Chiea Chuen

AU - Tai, E. Shyong

AU - Aung, Tin

AU - Vithana, Eranga

AU - Tay, Wan Ting

AU - Barathi, Veluchamy A.

AU - Chen, Peng

AU - Li, Ruoying

AU - Liao, Jiemin

AU - Zheng, Yingfeng

AU - Ong, Rick T.

AU - Döring, Angela

AU - Evans, David M.

AU - Timpson, Nicholas J.

AU - Verkerk, Annemieke J.M.H.

AU - Meitinger, Thomas

AU - Raitakari, Olli

AU - Hawthorne, Felicia

AU - Spector, Tim D.

AU - Karssen, Lennart C.

AU - Pirastu, Mario

AU - Murgia, Federico

AU - Ang, Wei

AU - Mishra, Aniket

AU - Montgomery, Grant W.

AU - Pennell, Craig E.

AU - Cumberland, Phillippa M.

AU - Cotlarciuc, Ioana

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Schache, Maria

AU - Janmahasathian, Sarayut

AU - Igo, Robert P.

AU - Lass, Jonathan H.

AU - Chew, Emily

AU - Iyengar, Sudha K.

AU - Gorgels, Theo G.M.F.

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Wright, Alan F.

AU - Polasek, Ozren

AU - Vatavuk, Zoran

AU - Wilson, James F.

AU - Fleck, Brian

AU - Zeller, Tanja

AU - Mirshahi, Alireza

AU - Müller, Christian

AU - Uitterlinden, André G.

AU - Rivadeneira, Fernando

AU - Vingerling, Johannes R.

AU - Hofman, Albert

AU - Oostra, Ben A.

AU - Amin, Najaf

AU - Bergen, Arthur A.B.

AU - Teo, Yik Ying

AU - Rahi, Jugnoo S.

AU - Vitart, Veronique

AU - Williams, Cathy

AU - Baird, Paul N.

AU - Wong, Tien Yin

AU - Oexle, Konrad

AU - Pfeiffer, Norbert

AU - Mackey, David A.

AU - Young, Terri L.

AU - Van Duijn, Cornelia M.

AU - Saw, Seang Mei

AU - Bailey-Wilson, Joan E.

AU - Stambolian, Dwight

AU - Klaver, Caroline C.

AU - Hammond, Christopher J.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

AB - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

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JO - Nature Genetics

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