Abstract
High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16 (ADAMTS16) and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z (PIGZ) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes (p = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (p = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of Data and Materials
The datasets generated and/or analyzed during the present study are not publicly available (obtained from Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai repository), but are available from the corresponding author upon reasonable request.
References
Ahmed I, Rasool S, Jan T, Qureshi T, Naykoo NA, Andrabi KI (2014) TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population. Curr Eye Res 39:282–290. https://doi.org/10.3109/02713683.2013.841950
Aldahmesh MA, Khan AO, Mohamed JY, Alkuraya H, Ahmed H, Bobis S, Al-Mesfer S, Alkuraya FS (2011) Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J Med Genet 48:597–601. https://doi.org/10.1136/jmedgenet-2011-100306
Aldahmesh MA, Alshammari MJ, Khan AO, Mohamed JY, Alhabib FA, Alkuraya FS (2013) The syndrome of microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) is caused by mutations in ADAMTS18. Hum Mutant 34:1195–1199. https://doi.org/10.1002/humu.22374
Boutin TS, Charteris DG, Chandra A, Campbell S, Hayward C, Campbell A, Nandakumar P, Hinds D, Mitry D, Vitart V (2020) Insights into the genetic basis of retinal detachment. Hum Mol Genet 29:689–702. https://doi.org/10.1093/hmg/ddz294
Cai XB, Shen SR, Chen DF, Zhang Q, Jin ZB (2019) An overview of myopia genetics. Exp Eye Res 188:107778. https://doi.org/10.1016/j.exer.2019.107778
Chandra A, Aragon-Martin JA, Hughes K, Gati S, Reddy MA, Deshpande C, Cormack G, Child AH, Charteris DG, Arno G (2012) A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis. Invest Ophthalmol vis Sci 53:4889–4896. https://doi.org/10.1167/iovs.12-9874
Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, MacGregor S, Verhoeven VJ, Barathi VA, Liao J, Hysi PG et al (2013) Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. Am J Hum Genet 93:264–277. https://doi.org/10.1016/j.ajhg.2013.06.016
Collin GB, Hubmacher D, Charette JR, Hicks WL, Stone L, Yu M, Naggert JK, Krebs MP, Peachey NS, Apte SS, Nishina PM (2015) Disruption of murine Adamtsl4 results in zonular fiber detachment from the lens and in retinal pigment epithelium dedifferentiation. Hum Mol Genet 24:6958–6974. https://doi.org/10.1093/hmg/ddv399
Dai L, Yang W, Qin X, Li Y, Cao H, Zhou C, Wang Y (2019) Serum metabolomics profiling and potential biomarkers of myopia using LC-QTOF/MS. Exp Eye Res 186:107737. https://doi.org/10.1016/j.exer.2019.107737
Dennis GJ, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:1–11. https://doi.org/10.1186/gb-2003-4-9-r60
Dirani M, Shekar SN, Baird PN (2008) Evidence of shared genes in refraction and axial length: the Genes in Myopia (GEM) twin study. Invest Ophthalmol vis Sci 49:4336–4339. https://doi.org/10.1167/iovs.07-1516
Dubail J, Apte SS (2015) Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics. Matrix Biol 44–46:24–37. https://doi.org/10.1016/j.matbio.2015.03.001
Duitama M, Vargas-López V, Casas Z, Albarracin SL, Sutachan JJ, Torres YP (2020) TRP channels role in pain associated with neurodegenerative diseases. Front Neurosci 14:782. https://doi.org/10.3389/fnins.2020.00782
Fan Q, Barathi VA, Cheng CY, Zhou X, Meguro A, Nakata I, Khor CC, Goh LK, Li YJ, Lim W, Ho CE, Hawthorne F, Zheng Y, Chua D, Inoko H, Yamashiro K, Ohno-Matsui K, Matsuo K, Matsuda F, Vithana E, Seielstad M, Mizuki N, Beuerman RW, Tai ES, Yoshimura N, Aung T, Young TL, Wong TY, Teo YY, Saw SM (2012) Genetic variants on chromosome 1q41 influence ocular axial length and high myopia. PLoS Genet 8:e1002753. https://doi.org/10.1371/journal.pgen.1002753
Fan Q, Wojciechowski R, Kamran IM, Cheng CY, Chen P, Zhou X, Pan CW, Khor CC, Tai ES, Aung T, Wong TY, Teo YY, Saw SM (2014) Education influences the association between genetic variants and refractive error: a meta-analysis of five Singapore studies. Hum Mol Genet 23:546–554. https://doi.org/10.1093/hmg/ddt431
Fang D, Zhang Z, Wei Y, Wang L, Zhang T, Jiang X, Shi Y, Zhang S (2020) The morphological relationship between dome-shaped macula and myopic retinoschisis: a cross-sectional study of 409 highly myopic eyes. Invest Ophthalmol vis Sci 61:19. https://doi.org/10.1167/iovs.61.3.19
Flaxman SR, Bourne R, 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 (2017) Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health 5:e1221–e1234. https://doi.org/10.1016/S2214-109X(17)30393-5
Hawthorne F, Feng S, Metlapally R, Li YJ, Tran-Viet KN, Guggenheim JA, Malecaze F, Calvas P, Rosenberg T, Mackey DA, Venturini C, Hysi PG, Hammond CJ, Young TL (2013) Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2. Invest Ophthalmol vis Sci 54:2076–2086. https://doi.org/10.1167/iovs.12-11102
Helisalmi S, Immonen I, Losonczy G, Resch MD, Benedek S, Balogh I, Papp A, Berta A, Uusitupa M, Hiltunen M, Kaarniranta K (2014) ADAMTS9 locus associates with increased risk of wet AMD. Acta Ophthalmol 92:e410. https://doi.org/10.1111/aos.12341
Hendriks M, Verhoeven V, Buitendijk G, Polling JR, Meester-Smoor MA, Hofman A, Kamermans M, Ingeborgh VDBL, Klaver C (2017) Development of refractive errors-what can we learn from inherited retinal dystrophies? Am J Ophthalmol 182:81–89. https://doi.org/10.1016/j.ajo.2017.07.008
Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, Wong TY, Naduvilath TJ, Resnikoff S (2016) Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 123:1036–1042. https://doi.org/10.1016/j.ophtha.2016.01.006
Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13. https://doi.org/10.1093/nar/gkn923
Hubmacher D, Apte SS (2015) ADAMTS proteins as modulators of microfibril formation and function. Matrix Biol 47:34–43. https://doi.org/10.1016/j.matbio.2015.05.004
Hysi PG, Choquet H, Khawaja AP, Wojciechowski R, Tedja MS, Yin J, Simcoe MJ, Patasova K, Mahroo OA, Thai KK, Cumberland PM, Melles RB, Verhoeven V, Vitart V, Segre A, Stone RA, Wareham N, Hewitt AW, Mackey DA, Klaver C, MacGregor S, Khaw PT, Foster PJ, Guggenheim JA, Rahi JS, Jorgenson E, Hammond CJ (2020) Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat Genet 52:401–407. https://doi.org/10.1038/s41588-020-0599-0
Jin ZB, Wu J, Huang XF, Feng CY, Cai XB, Mao JY, Xiang L, Wu KC, Xiao X, Kloss BA, Li Z, Liu Z, Huang S, Shen M, Cheng FF, Cheng XW, Zheng ZL, Chen X, Zhuang W, Zhang Q, Young TL, Xie T, Lu F, Qu J (2017) Trio-based exome sequencing arrests de novo mutations in early-onset high myopia. Proc Natl Acad Sci U S A 114:4219–4224. https://doi.org/10.1073/pnas.1615970114
Jonas JB, Wang YX, Dong L, Guo Y, Panda-Jonas S (2020) Advances in myopia research anatomical findings in highly myopic eyes. Eye vis (Lond) 7:45. https://doi.org/10.1186/s40662-020-00210-6
Kempen JH, Mitchell P, Lee KE, Tielsch JM, Broman AT, Taylor HR, Ikram MK, Congdon NG, O’Colmain BJ (2004) The prevalence of refractive errors among adults in the United States, Western Europe, and Australia. Arch Ophthalmol 122:495–505. https://doi.org/10.1001/archopht.122.4.495
Li J, Jiang D, Xiao X, Li S, Jia X, Sun W, Guo X, Zhang Q (2015) Evaluation of 12 myopia-associated genes in Chinese patients with high myopia. Invest Ophthalmol vis Sci 56:722–729. https://doi.org/10.1167/iovs.14-14880
Li Z, Liu R, Xiao O, Guo X, Wang D, Zhang J, Ha JJ, Lee J, Lee P, Jong M, Sankaridurg P, Ohno-Matsui K, He M (2019) Progression of myopic maculopathy in highly myopic chinese eyes. Invest Ophthalmol vis Sci 60:1096–1104. https://doi.org/10.1167/iovs.18-25800
Lin Y, Ding Y, Jiang D, Li C, Huang X, Liu L, Xiao H, Vasudevan B, Chen Y (2020) Genome-wide association of genetic variants with refraction, axial length, and corneal curvature: a longitudinal study of Chinese schoolchildren. Front Genet 11:276. https://doi.org/10.3389/fgene.2020.00276
Liu J, Zhang R, Sun L, Zheng Y, Chen S, Chen SL, Xu Y, Pang CP, Zhang M, Ng TK (2019) Genotype-phenotype correlation and interaction of 4q25, 15q14 and MIPEP variants with myopia in southern Chinese population. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2019-314782
Lu SY, Tang SM, Li FF, Kam KW, Tam P, Yip W, Young AL, Tham CC, Pang CP, Yam JC, Chen LJ (2020) Association of WNT7B and RSPO1 with axial length in school children. Invest Ophthalmol vis Sci 61:11. https://doi.org/10.1167/iovs.61.10.11
Markov PP, Eliasy A, Pijanka JK, Htoon HM, Paterson NG, Sorensen T, Elsheikh A, Girard M, Boote C (2018) Bulk changes in posterior scleral collagen microstructure in human high myopia. Mol vis 24:818–833
Meguro A, Yamane T, Takeuchi M, Miyake M, Fan Q, Zhao W, Wang IJ, Mizuki Y, Yamada N, Nomura N, Tsujikawa A, Matsuda F, Hosoda Y, Saw SM, Cheng CY, Tsai TH, Yoshida M, Iijima Y, Teshigawara T, Okada E, Ota M, Inoko H, Mizuki N (2020) Genome-wide association study in asians identifies novel loci for high myopia and highlights a nervous system role in its pathogenesis. Ophthalmology 127:1612–1624. https://doi.org/10.1016/j.ophtha.2020.05.014
Meng W, Butterworth J, Malecaze F, Calvas P (2011) Axial length of myopia: a review of current research. Ophthalmologica 225:127–134. https://doi.org/10.1159/000317072
Meng W, Butterworth J, Bradley DT, Hughes AE, Soler V, Calvas P, Malecaze F (2012) A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population. Invest Ophthalmol vis Sci 53:7983–7988. https://doi.org/10.1167/iovs.12-10409
Miyake M, Yamashiro K, Tabara Y, Suda K, Morooka S, Nakanishi H, Khor CC, Chen P, Qiao F, Nakata I, Akagi-Kurashige Y, Gotoh N, Tsujikawa A, Meguro A, Kusuhara S, Polasek O, Hayward C, Wright AF, Campbell H, Richardson AJ, Schache M, Takeuchi M, Mackey DA, Hewitt AW, Cuellar G, Shi Y, Huang L, Yang Z, Leung KH, Kao P, Yap M, Yip SP, Moriyama M, Ohno-Matsui K, Mizuki N, MacGregor S, Vitart V, Aung T, Saw SM, Tai ES, Wong TY, Cheng CY, Baird PN, Yamada R, Matsuda F, Yoshimura N (2015) Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia. Nat Commun 6:6689. https://doi.org/10.1038/ncomms7689
Morrison JC, L’Hernault NL, Jerdan JA, Quigley HA (1989) Ultrastructural location of extracellular matrix components in the optic nerve head. Arch Ophthalmol 107:123–129. https://doi.org/10.1001/archopht.1989.01070010125040
Nakanishi H, Yamada R, Gotoh N, Hayashi H, Yamashiro K, Shimada N, Ohno-Matsui K, Mochizuki M, Saito M, Iida T, Matsuo K, Tajima K, Yoshimura N, Matsuda F (2009) A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1. PLoS Genet 5:e1000660. https://doi.org/10.1371/journal.pgen.1000660
Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12:218. https://doi.org/10.1186/gb-2011-12-3-218
Ohno-Matsui K, Lai TY, Lai CC, Cheung CM (2016) Updates of pathologic myopia. Prog Retin Eye Res 52:156–187. https://doi.org/10.1016/j.preteyeres.2015.12.001
Pan CW, Zheng YF, Anuar AR, Chew M, Gazzard G, Aung T, Cheng CY, Wong TY, Saw SM (2013) Prevalence of refractive errors in a multiethnic Asian population: the Singapore epidemiology of eye disease study. Invest Ophthalmol vis Sci 54:2590–2598. https://doi.org/10.1167/iovs.13-11725
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575. https://doi.org/10.1086/519795
Riddell N, Crewther SG (2017) Integrated comparison of GWAS, transcriptome, and proteomics studies highlights similarities in the biological basis of animal and human myopia. Invest Ophthalmol vis Sci 58:660–669. https://doi.org/10.1167/iovs.16-20618
Saw SM, Chua WH, Wu HM, Yap E, Chia KS, Stone RA (2000) Myopia: gene-environment interaction. Ann Acad Med Singapore 29:290–297
Schache M, Richardson AJ, Mitchell P, Wang JJ, Rochtchina E, Viswanathan AC, Wong TY, Saw SM, Topouzis F, Xie J, Sim X, Holliday EG, Attia J, Scott RJ, Baird PN (2013) Genetic association of refractive error and axial length with 15q14 but not 15q25 in the Blue Mountains Eye Study cohort. Ophthalmology 120:292–297. https://doi.org/10.1016/j.ophtha.2012.08.006
Schaeffel F, Burkhardt E, Howland HC, Williams RW (2004) Measurement of refractive state and deprivation myopia in two strains of mice. Optom vis Sci 81:99–110. https://doi.org/10.1097/00006324-200402000-00008
Schellevis RL, Breukink MB, Gilissen C, Boon C, Hoyng CB, de Jong EK, den Hollander AI (2019) Exome sequencing in patients with chronic central serous chorioretinopathy. Sci Rep 9:6598. https://doi.org/10.1038/s41598-019-43152-3
Shah RL, Guggenheim JA (2018) Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci. Hum Genet 137:881–896. https://doi.org/10.1007/s00439-018-1942-8
Stone RA, Pardue MT, Iuvone PM, Khurana TS (2013) Pharmacology of myopia and potential role for intrinsic retinal circadian rhythms. Exp Eye Res 114:35–47. https://doi.org/10.1016/j.exer.2013.01.001
Stone RA, McGlinn AM, Chakraborty R, Lee DC, Yang V, Elmasri A, Landis E, Shaffer J, Iuvone PM, Zheng X, Sehgal A, Pardue MT (2019) Altered ocular parameters from circadian clock gene disruptions. PLoS ONE 14:e0217111. https://doi.org/10.1371/journal.pone.0217111
Stone RA, Wei W, Sarfare S, McGeehan B, Engelhart KC, Khurana TS, Maguire MG, Iuvone PM, Nickla DL (2020) Visual image quality impacts circadian rhythm-related gene expression in retina and in choroid: a potential mechanism for ametropias. Invest Ophthalmol vis Sci 61:13. https://doi.org/10.1167/iovs.61.5.13
Tedja MS, Wojciechowski R, Hysi PG, Eriksson N, Furlotte NA, Verhoeven V, Iglesias AI, Meester-Smoor MA, Tompson SW, Fan Q, Khawaja AP, Cheng CY, 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 B, Klein R, Paterson AD, Hosseini SM, Shah RL, Williams C, Teo YY, Tham YC, Gupta P, Zhao W, Shi Y, Saw WY, Tai ES, Sim XL, Huffman JE, Polašek O, Hayward C, Bencic G, Rudan I, Wilson JF, 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 TH, Igo RJ, 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 SM, Stambolian D, MacGregor S, Guggenheim JA, Tung JY, Hammond CJ, Klaver C (2018) Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nat Genet 50:834–848. https://doi.org/10.1038/s41588-018-0127-7
Tedja MS, Haarman A, Meester-Smoor MA, Kaprio J, Mackey DA, Guggenheim JA, Hammond CJ, Verhoeven V, Klaver C (2019) IMI—myopia genetics report. Invest Ophthalmol vis Sci 60:M89–M105. https://doi.org/10.1167/iovs.18-25965
Tran H, Tran YH, Tran TD, Jong M, Coroneo M, Sankaridurg P (2018) A review of myopia control with atropine. J Ocul Pharmacol Ther 34:374–379. https://doi.org/10.1089/jop.2017.0144
Wu XH, Li YY, Zhang PP, Qian KW, Ding JH, Hu G, Weng SJ, Yang XL, Zhong YM (2015) Unaltered retinal dopamine levels in a C57BL/6 mouse model of form-deprivation myopia. Invest Ophthalmol vis Sci 56:967–977. https://doi.org/10.1167/iovs.13-13362
Xu L, Li J, Cui T, Hu A, Fan G, Zhang R, Yang H, Sun B, Jonas JB (2005) Refractive error in urban and rural adult Chinese in Beijing. Ophthalmology 112:1676–1683. https://doi.org/10.1016/j.ophtha.2005.05.015
Yang H, Wang K (2015) Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc 10:1556–1566. https://doi.org/10.1038/nprot.2015.105
Yi H, Zha X, Zhu Y, Lv J, Hu S, Kong Y, Wu G, Yang Y, He Y (2019) A novel nonsense mutation in ADAMTS17 caused autosomal recessive inheritance Weill-Marchesani syndrome from a Chinese family. J Hum Genet 64:681–687. https://doi.org/10.1038/s10038-019-0608-2
Yoneyama S, Sakurada Y, Kikushima W, Sugiyama A, Matsubara M, Fukuda Y, Tanabe N, Parikh R, Mabuchi F, Kashiwagi K, Iijima H (2020) Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Sci Rep 10:7188. https://doi.org/10.1038/s41598-020-64301-z
You QS, Wu LJ, Duan JL, Luo YX, Liu LJ, Li X, Gao Q, Wang W, Xu L, Jonas JB, Guo XH (2014) Prevalence of myopia in school children in greater Beijing: the Beijing Childhood Eye Study. Acta Ophthalmol 92:e398-406. https://doi.org/10.1111/aos.12299
Younan C, Mitchell P, Cumming RG, Rochtchina E, Wang JJ (2002) Myopia and incident cataract and cataract surgery: the Blue Mountains Eye Study. Invest Ophthalmol vis Sci 43:3625–3632
Young TL, Ronan SM, Drahozal LA, Wildenberg SC, Alvear AB, Oetting WS, Atwood LD, Wilkin DJ, King RA (1998) Evidence that a locus for familial high myopia maps to chromosome 18p. Am J Hum Genet 63:109–119. https://doi.org/10.1086/301907
Acknowledgements
Publication of this article was supported by research grants from the National Natural Science Foundation of China (No.82122017, 81870642, 81970780 and 81670835), Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission (No. 19441900700 and No.21S31904900), Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center (No. SHDC12019X08 and SHDC2020CR4078), Double-E Plan of Eye & ENT Hospital (SYA202006), and Shanghai Municipal Key Clinical Specialty Program (shslczdzk01901).
Funding
Funding was provided by the National Natural Science Foundation of China, 82122017: Xiangjia Zhu, 81970780: Yi Lu, 81870642: Xiangjia Zhu, 81670835: Yi Lu; Science and Technology Innovation Plan of Shanghai Science and Technology Commission, 19441900700: Xiangjia Zhu, 21S31904900: Xiangjia Zhu; Shanghai Hospital Development Center, SHDC12019X08: Xiangjia Zhu; Shanghai Shenkang Hospital Development Center, SHDC2020CR4078: Xiangjia Zhu; Double-E Plan of Eye & ENT Hospital, SYA202006: Xiangjia Zhu; Shanghai Municipal Key Clinical Specialty Program, shslczdzk01901: Xiangjia Zhu.
Author information
Authors and Affiliations
Contributions
Study concept and design: QL, YD, YZ, HL, XZ, YL; data collection: QL, YD, WH, YT, ZZ,YZ; analysis and interpretation of data: QL, YZ, JW, XZ; writing the manuscript: QL, HL; critical revision of the manuscript: QL, YC, XZ, YL; administrative, technical, or material support: JW, YL; supervision: YT, XZ, YL.
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ethics Approval
The Institutional Review Board of the Eye and ENT Hospital of Fudan University, Shanghai, China, as well as MGI-Shenzhen, approved this study. All procedures adhered to the Declaration of Helsinki and were conducted in accordance with the approved protocol. Animal experiments were approved by the Eye and ENT Hospital of Fudan University, and were conducted according to the Association of Research in Vision and Ophthalmology Statement for the use of animals in Ophthalmology and Vision Research.
Consent to Participate
Written informed consent forms were signed by all patients before the collection of peripheral blood and clinical data.
Consent for Publication
All the participants approved to publishing this work.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Lu, Q., Du, Y., Zhang, Y. et al. A Genome-Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes. Phenomics 3, 255–267 (2023). https://doi.org/10.1007/s43657-022-00082-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43657-022-00082-x