The Influence of Genetics in Myopia Control: A Pilot Study
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Design and Approval of the Ethics Committee
2.2. Selection of SNPs
2.3. Study Population and Inclusion Criteria
2.4. Clinical Procedure
2.5. Statistical Analysis
3. Results
3.1. Clinical and Demographic Characteristics
3.2. Allele and Genotypic Frequencies
3.2.1. AL/CR
3.2.2. SE
3.3. Haplotype Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Morgan, I.G.; Ohno-Matsui, K.; Saw, S.M. Myopia. Lancet 2012, 379, 1739–1748. [Google Scholar] [CrossRef]
- Ang, M.; Wong, T.Y. Updates on Myopia, 1st ed.; Springer: Singapore, 2020. [Google Scholar]
- Liao, X.; Yap, M.K.H.; Leung, K.H.; Kao, P.Y.P.; Liu, L.Q.; Yip, S.P. Genetic Association Study of KCNQ5 Polymorphisms with High Myopia. BioMed Res. Int. 2017, 2017, 3024156. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tedja, M.S.; Haarman, A.E.G.; Meester-Smoor, M.A.; Kaprio, J.; Mackey, D.A.; Guggenheim, J.A.; Hammond, C.J.; Verhoeven, V.J.M.; Klaver, C.C.W.; CREAM Consortium. IMI—Myopia Genetics Report. Investig. Opthalmol. Vis. Sci. 2019, 60, M89–M105. [Google Scholar] [CrossRef] [Green Version]
- Verhoeven, V.J.; Hysi, P.G.; Wojciechowski, R.; Fan, Q.; Guggenheim, J.A.; Höhn, R.; MacGregor, S.; Hewitt, A.W.; Nag, A.; Cheng, C.-Y.; et al. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat. Genet. 2013, 45, 314–318. [Google Scholar] [CrossRef] [PubMed]
- Kiefer, A.K.; Tung, J.Y.; Do, C.; Hinds, D.A.; Mountain, J.L.; Francke, U.; Eriksson, N. Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia. PLoS Genet. 2013, 9, e1003299. [Google Scholar] [CrossRef] [Green Version]
- Tideman, J.W.; Fan, Q.; Polling, J.R.; Guo, X.; Yazar, S.; Khawaja, A.; Höhn, R.; Lu, Y.; Jaddoe, V.W.; Yamashiro, K.; et al. When do myopia genes have their effect? Comparison of genetic risks between children and adults. Genet. Epidemiol. 2016, 40, 756–766. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tedja, M.S.; Wojciechowski, R.; Hysi, P.G.; Eriksson, N.; Furlotte, N.A.; Verhoeven, V.J.M.; Iglesias, A.I.; Meester-Smoor, M.A.; Tompson, S.W.; Fan, Q.; et al. Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nat. Genet. 2018, 50, 834–848. [Google Scholar] [CrossRef]
- Hysi, P.G.; Choquet, H.; Khawaja, A.P.; Wojciechowski, R.; Tedja, M.S.; Yin, J.; Simcoe, M.J.; Patasova, K.; Mahroo, O.A.; Thai, K.K.; et al. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat. Genet. 2020, 52, 401–407. [Google Scholar] [CrossRef]
- Wildsoet, C.F.; Chia, A.; Cho, P.; Guggenheim, J.A.; Polling, J.R.; Read, S.; Sankaridurg, P.; Saw, S.-M.; Trier, K.; Walline, J.J.; et al. IMI—Interventions Myopia Institute: Interventions for Controlling Myopia Onset and Progression Report. Investig. Opthalmol. Vis. Sci. 2019, 60, M106–M131. [Google Scholar] [CrossRef] [Green Version]
- Ruiz-Pomeda, A.; Pérez-Sánchez, B.; Valls, I.; Prieto-Garrido, F.L.; Gutiérrez-Ortega, R.; Villa-Collar, C. MiSight Assessment Study Spain (MASS). A 2-year randomized clinical trial. Graefe’s Arch. Clin. Exp. Ophthalmol. 2018, 256, 1011–1021. [Google Scholar] [CrossRef]
- Solé, X.; Guinó, E.; Valls, J.; Iniesta, R.; Moreno, V. SNPStats: A web tool for the analysis of association studies. Bioinformatics 2006, 22, 1928–1929. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barrett, J.C.; Fry, B.; Maller, J.; Daly, M.J. Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21, 263–265. [Google Scholar] [CrossRef] [Green Version]
- Tideman, J.W.L.; Polling, J.R.; Vingerling, J.R.; Jaddoe, V.W.V.; Williams, C.; Guggenheim, J.A.; Klaver, C.C.W. Axial length growth and the risk of developing myopia in European children. Acta Ophthalmol. 2017, 96, 301–309. [Google Scholar] [CrossRef] [PubMed]
- Hysi, P.G.; Mahroo, O.A.; Cumberland, P.; Wojciechowski, R.; Williams, K.M.; Young, T.L.; Mackey, D.A.; Rahi, J.S.; Hammond, C.J. Common mechanisms underlying refractive error identified in functional analysis of gene lists from genome-wide association study results in 2 European British cohorts. JAMA Ophthalmol. 2014, 132, 50–56. [Google Scholar] [CrossRef] [Green Version]
- Chandra, A.; Mitry, D.; Wright, A.; Campbell, H.; Charteris, D.G. Genome-wide association studies: Applications and insights gained in Ophthalmology. Eye 2014, 28, 1066–1079. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Troilo, D.; Smith, E.L., 3rd; Nickla, D.L.; Ashby, R.; Tkatchenko, A.V.; Ostrin, L.A.; Gawne, T.J.; Pardue, M.T.; Summers, J.A.; Kee, C.-S.; et al. IMI—Report on experimental models of emmetropization and myopia. Investig. Opthalmol. Vis. Sci. 2019, 60, M31–M88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harper, A.R.; Summers, J.A. The dynamic sclera: Extracellular matrix remodeling in normal ocular growth and myopia development. Exp. Eye Res. 2015, 133, 100–111. [Google Scholar] [CrossRef] [Green Version]
- Hung, G.K.; Mahadas, K.; Mohammad, F. Eye growth and myopia development: Unifying theory and Matlab model. Comput. Biol. Med. 2016, 70, 106–118. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Wu, J.; Cui, D.; Zeng, J. Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs. Mol. Med. Rep. 2016, 13, 2671–2676. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Liu, Y.; Wildsoet, C.F. Bidirectional, optical sign-dependent regulation of bmp2 gene expression in chick retinal pigment epithelium. Investig. Opthalmol. Vis. Sci. 2012, 53, 6072–6080. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sakuta, H.; Takahashi, H.; Shintani, T.; Etani, K.; Aoshima, A.; Noda, M. Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection. J. Neurosci. 2006, 26, 10868–10878. [Google Scholar] [CrossRef] [PubMed]
- Ueki, Y.; Reh, T.A. Activation of BMP-Smad1/5/8 signaling promotes survival of retinal ganglion cells after damage In Vivo. PLoS ONE 2012, 7, e38690. [Google Scholar] [CrossRef]
- Ueki, Y.; Reh, T.A. EGF stimulates müller glial proliferation via a BMP-dependent mechanism. Glia 2013, 61, 778–789. [Google Scholar] [CrossRef] [Green Version]
- Mathura, J.R., Jr.; Jafari, N.; Chang, J.T.; Hackett, S.F.; Wahlin, K.J.; Della, N.G.; Okamoto, N.; Zack, D.J.; Campochiaro, P.A. Bone morphogenetic proteins-2 and -4: Negative growth regulators in adult retinal pigmented epithelium. Investig. Ophthalmol. Vis. Sci. 2000, 41, 592–600. [Google Scholar]
- Simpson, C.L.; Wojciechowski, R.; Oexle, K.; Murgia, F.; Portas, L.; Li, X.; Verhoeven, V.J.M.; Vitart, V.; Schache, M.; Hosseini, S.M.; et al. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci. PLoS ONE 2014, 9, e107110. [Google Scholar] [CrossRef] [Green Version]
- Paylakhi, S.; Labelle-Dumais, C.; Tolman, N.G.; Sellarole, M.A.; Seymens, Y.; Saunders, J.; Lakosha, H.; Devries, W.N.; Orr, A.C.; Topilko, P.; et al. Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error. PLoS Genet. 2018, 14, e1007244. [Google Scholar] [CrossRef]
- Yoshikawa, M.; Yamashiro, K.; Miyake, M.; Oishi, M.; Akagi-Kurashige, Y.; Kumagai, K.; Nakata, I.; Nakanishi, H.; Oishi, A.; Gotoh, N.; et al. Comprehensive replication of the relationship between myopia-related genes and refractive errors in a large japanese cohort. Investig. Opthalmol. Vis. Sci. 2014, 55, 7343–7354. [Google Scholar] [CrossRef]
- Kinane, D.; Hart, T. Genes and gene polymorphisms associated with periodontal disease. Crit. Rev. Oral Biol. Med. 2003, 14, 430–449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Gene | Locus | OMIM | SNP | Cambio | MAF | Beta Effect (SE) * | p * |
---|---|---|---|---|---|---|---|
GJD2 | 15q14 | 607058 | rs524952 | T > A | A: 0,471 | 0.0069 (0.0016) | 10−5 |
ZIC2 | 13q32.3 | 603073 | rs8000973 | T > C | T: 0,475 | 0.0058 (0.0017) | 10−4 |
CHRNG | 2q37.1 | 100730 | rs1881492 | T > G | T: 0,224 | 0.0086 (0.0024) | 10−4 |
PRSS56 | 2q37.1 | 613858 | rs1656404 | G > A | A: 0,220 | 0.0073 (0.0024) | 0.002 |
KCNQ5 | 6q13 | 607357 | rs7744813 | A > C | C: 0,380 | 0.0050 (0.0017) | 0.004 |
SHISA6 | 17p12 | 617327 | rs2969180 | G > A | A: 0,357 | 0.0035 (0.0016) | 0.03 |
KCNMA1 | 10q22.3 | 600150 | rs6480859 | C > T | T: 0,362 | 0.0040 (0.0018) | 0.02 |
BMP2 | 20p12.3 | 112261 | rs235770 | T > C | T: 0,379 | 0.0043 (0.0018) | 0.02 |
Parameter | Responder (n = 15) | Nonresponder (n = 13) | p-Value * |
---|---|---|---|
Gender (n, %) | Female 8 (46.67) Male 7 (53.33) | Female 9 (69.23) Male 4 (30.77) | 0.390 |
Age (mean ± SD, years) | 17.47 ± 1.36 | 17.00 ± 1.63 | 0.416 |
AL (mean ± SD, mm) | Right: 24.57 ± 0.70 Left: 24.52 ± 0.75 Mean: 24.45 ± 0.71 | Right: 25.23 ± 0.55 Left: 25.17 ± 0.53 Mean: 25.20 ± 0.53 | 0.011 0.014 0.011 |
SE (mean ± SD, D) | Right: −2.71 ± −1.41 Left: −2.55 ± 1.35 Mean: −2.62 ± 1.35 | Right: −3.80 ± −1.48 Left: −4.16 ± 1.60 Mean: −3.98 ± 1.50 | 0.056 0.008 0.019 |
AL/CR (mean ± SD, mm) | Right: 0.58 ± 0.04 Left: 0.57 ± 0.04 Mean: 0.58 ± 0.01 | Right: 0.60 ± 0.04 Left: 0.60 ± 0.04 Mean: 0.60 ± 0.01 | 0.071 0.059 0.064 |
Myopia degree (n, %) | Low myopia: 9 (63.3) Moderate myopia: 6 (36.7) High myopia: 0 (0) | Low myopia: 2 (19.2) Moderate myopia: 9 (65.4) High myopia: 2 (15.4) | 0.001 |
Gene | SNP | Locus | Allele | MAF | Risk Allele | Risk Allele Frequency (%) | HWE p | p-Value | OR (95% CI) | |
---|---|---|---|---|---|---|---|---|---|---|
Res | N. Res | |||||||||
ZIC2 | rs8000973 | 13q32.3 | T > C | 0.446 | T | 12 (0.40) | 13 (0.50) | 0.72 | 0.61 | 1.44 (0.35–5.92) |
KCNQ5 | rs7744813 | 6q13 | A > C | 0.250 | C | 10 (0.33) | 4 (0.15) | 0.65 | 0.26 | 2.43 (0.50–11.75) |
GJD2 | rs524952 | 15q14 | T > A | - | . | . | . | 0.056 | 0.24 | 2.75 (0.48–15.57) |
CHRNG | rs1881492 | 2q37.1 | T > G | 0.107 | T | 2 (0.07) | 4 (0.15) | 1 | 0.29 | 0.32 (0.04–2.81) |
PRSS56 | rs1656404 | 2q37.1 | G > A | 0.125 | A | 4 (0.13) | 3 (0.12) | 1 | 0.95 | 0.94 (0.12–7.38) |
BMP2 | rs235770 | 20p12.3 | T > C | 0.375 | T | 15 (0.5) | 6 (0.23) | 0.43 | 0.049 | 3.37 (1.079–10.886) |
Gene. (SNP) | Models of Heredity–Frequency (%) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Additive | Dominant | Recessive | |||||||||||||
Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | |
ZIC2 (rs8000973) | C/C C/T T/T | 5 (33.3) 8 (53.3) 2 (13.3) | 4 (30.8) 5 (38.5) 4 (30.8) | 0.48 | 1.00 4.31 (0.34–54.43) 2.32 (0.12–43.22) | C/C T/C + T/T | 5 (33.3) 10 (66.7) | 4 (30.8%) 9 (69.2%) | 0.28 | 1.00 3.62 (0.32-40.86) | C/C + T/C T/T | 13 (86.7) 2 (13.3) | 9 (69.2) 4 (30.8) | 0.81 | 1.00 0.77 (0.09–6.66) |
KCNQ5 (rs7744813) | A/A A/C C/C | 6 (40.0) 8 (53.3) 1 (6.7) | 9 (69.2) 4 (30.8) 0 (0) | 0.45 | 1.00 2.08 (0.37–11.52) NA (0.00–NA) | A/A A/C + C/C | 6 (40.0) 9 (60.0) | 9 (69.2) 4 (30.8) | 0.33 | 1.00 2.33 (0.43-12.66) | A/A + A/C C/C | 14 (93.3) 1 (6.7) | 13 (100.0) 0 (0.0) | 0.34 | 1.00 NA (0.00–NA) |
GJD2 (rs524952) | A/A T/A T/T | 2 (13.3) 10 (66.7) 3 (20.0) | 2 (15.4) 10 (76.9) 1 (7.7) | 0.37 | 1.00 1.38 (0.12–16.22) 10.21 (0.25-416.37) | A/A T/A + T/T | 2 (13.3) 13 (86.7) | 2 (15.4) 11 (84.6) | 0.6 | 1.00 1.90 (0.18-20.46) | A/A+T/A T/T | 12 (80.0) 3 (20.0) | 12 (92.3) 1 (7.7) | 0.16 | 1.00 7.93 (0.34–182.43) |
CHRNG (rs1881492) | G/G G/T T/T | 13 (86.7) 2 (13.3) 0 (0.0) | 9 (69.2) 4 (30.8) 0 (0.0) | 0.29 | 1.00 0.32 (0.04–2.81) | - | - | - | - | - | - | - | - | - | - |
PRSS56 (rs1656404) | G/G G/A A/A | 11 (73.3) 4 (26.7) 0 (0.0) | 10 (76.9) 3 (23.1) 0 (0.0) | 0.95 | 1.00 0.94 (0.12–7.38) | - | - | - | - | - | - | - | - | - | - |
BMP2 (rs235770) | C/C C/T T/T | 4 (26.7) 7 (46.7) 4 (26.7) | 8 (61.5) 4 (30.8) 1 (7.7) | 0.11 | 1.00 1.87 (0.26–13.63) 19.09 (0.84–434.64) | C/C C/T + T/T | 4 (26.7) 11 (73.3) | 8 (61.5) 5 (38.5) | 0.15 | 1.00 3.58 (0.62–20.53) | C/C + C/T T/T | 11 (73.3) 4 (26.7) | 12 (92.3) 1 (7.7) | 0.043 | 1.00 15.19 (0.72–319.94) |
Gene | SNP | Locus | Allele | MAF | Risk Allele | Risk Allele Frequency (%) | HWE p | p-Value | OR (95% CI) | |
---|---|---|---|---|---|---|---|---|---|---|
Res | N. Res | |||||||||
ZIC2 | rs8000973 | 13q32.3 | T > C | 0.446 | T | 12 (0.40) | 13 (0.50) | 0.72 | 0.78 | 0.82 (0.22–3.16) |
KCNQ5 | rs7744813 | 6q13 | A > C | 0.250 | C | 10 (0.33) | 4 (0.15) | 0.65 | 0.33 | 2.49 (0.38–16.10) |
GJD2 | rs524952 | 15q14 | T > A | - | . | . | . | 0.056 | 0.52 | 1.78 (0.29–10.81) |
CHRNG | rs1881492 | 2q37.1 | T > G | 0.107 | T | 2 (0.07) | 4 (0.15) | 1 | 0.09 | 0.11 (0.01–1.73) |
PRSS56 | rs1656404 | 2q37.1 | G > A | 0.125 | A | 4 (0.13) | 3 (0.12) | 1 | 0.88 | 0.83 (0.08–9.09) |
BMP2 | rs235770 | 20p12.3 | T > C | 0.375 | T | 15 (0.5) | 6 (0.23) | 0.43 | 0.009 | 10.54 (1.00–111.38) |
Gene (SNP) | Models of Heredity–Frequency (%) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Additive | Dominant | Recessive | |||||||||||||
Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | Gn | Res n (%) | N. Res n (%) | p | OR (95% CI) | |
ZIC2 (rs8000973) | C/C C/T T/T | 5 (33.3) 8 (53.3) 2 (13.3) | 4 (30.8) 5 (38.5) 4 (30.8) | 0.85 | 1.00 1.53 (0.09–25.16) 0.74 (0.05–11.31) | C/C T/C+ T/T | 5 (33.3) 10 (66.7) | 4 (30.8%) 9 (69.2%) | 0.98 | 1.00 1.04 (0.09–12.06) | C/C + T/C T/T | 13 (86.7) 2 (13.3) | 9 (69.2) 4 (30.8) | 0.63 | 1.00 0.58 (0.06–5.24) |
KCNQ5 (rs7744813) | A/A A/C C/C | 6 (40.0) 8 (53.3) 1 (6.7) | 9 (69.2) 4 (30.8) 0 (0.0) | 0.61 | 1.00 2.42 (0.36–16.21) NA (0.00-NA) | A/A A/C + C/C | 6 (40.0) 9 (60.0) | 9 (69.2) 4 (30.8) | 0.34 | 1.00 2.48 (0.37–16.54) | A/A + A/C C/C | 14 (93.3) 1 (6.7) | 13 (100.0) 0 (0.0) | 0.72 | 1.00 NA (0.00-NA) |
GJD2 (rs524952) | A/A T/A T/T | 2 (13.3) 10 (66.7) 3 (20.0) | 2 (15.4) 10 (76.9) 1 (7.7) | 0.66 | 1.00 0.94 (0.07–13.35) 4.28 (0.09-205.58) | A/A T/A + T/T | 2 (13.3) 13 (86.7) | 2 (15.4) 11 (84.6) | 0.84 | 1.00 1.30 (0.10–16.37) | A/A + T/A T/T | 12 (80.0) 3 (20.0) | 12 (92.3) 1 (7.7) | 0.36 | 1.00 4.45 (0.15–135.65) |
CHRNG (rs1881492) | G/G G/T T/T | 13 (86.7) 2 (13.3) 0 (0.0) | 9 (69.2) 4 (30.8) 0 (0.0) | 0.085 | 1.00 0.11 (0.01–1.73) | - | - | - | - | - | - | - | - | - | - |
PRSS56 (rs1656404) | G/G G/A A/A | 11 (73.3) 4 (26.7) 0 (0.0) | 10 (76.9) 3 (23.1) 0 (0.0) | 0.88 | 1.00 0.83 (0.08–9.09) | - | - | - | - | - | - | - | - | - | - |
BMP2 (rs235770) | C/C C/T T/T | 4 (26.7) 7 (46.7) 4 (26.7) | 8 (61.5) 4 (30.8) 1 (7.7) | 0.028 | 1.00 5.99 (0.31-116.13) 168.90 (1.08–NA) | C/C C/T + T/T | 4 (26.7) 11 (73.3) | 8 (61.5) 5 (38.5) | 0.046 | 1.00 9.98 (0.78-127.69) | C/C + C/T T/T | 11 (73.3) 4 (26.7) | 12 (92.3) 1 (7.7) | 0.019 | 1.00 1.26 (0.519–57.169) |
Number of SNPs | Linkage Disequilibrium | r | p |
---|---|---|---|
SNP1–SNP6 | rs235770–rs8000973 | 0.1735 | 0.1941 |
SNP2–SNP6 | rs235770–rs7744813 | 0.0426 | 0.7496 |
SNP3–SNP6 | rs235770–rs524952 | 0.1540 | 0.2491 |
SNP4–SNP6 | rs235770–rs1881492 | −0.2678 | 0.0451 |
SNP5–SNP6 | rs235770–rs1656404 | −0.2925 | 0.0286 |
Haplotypes | Haplotype Frequency | OR (95% CI) | Haplotype Test | |
---|---|---|---|---|
Res | N. Res | p | ||
rs235770–rs1656404 | 0.00011 | |||
GC | 0.367 | 0.719 | 1.00 | - |
GT | 0.500 | 0.165 | 22.99 (2.50–211.11) | 0.008 |
AC | 0.135 | 0.050 | 5.06 (0.54–47.23) | 0.160 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Alvarez-Peregrina, C.; Sánchez-Tena, M.Á.; Martinez-Perez, C.; Santiago-Dorrego, C.; Yvert, T.; Andreu-Vazquez, C.; Villa-Collar, C. The Influence of Genetics in Myopia Control: A Pilot Study. J. Clin. Med. 2021, 10, 808. https://doi.org/10.3390/jcm10040808
Alvarez-Peregrina C, Sánchez-Tena MÁ, Martinez-Perez C, Santiago-Dorrego C, Yvert T, Andreu-Vazquez C, Villa-Collar C. The Influence of Genetics in Myopia Control: A Pilot Study. Journal of Clinical Medicine. 2021; 10(4):808. https://doi.org/10.3390/jcm10040808
Chicago/Turabian StyleAlvarez-Peregrina, Cristina, Miguel Ángel Sánchez-Tena, Clara Martinez-Perez, Catalina Santiago-Dorrego, Thomas Yvert, Cristina Andreu-Vazquez, and Cesar Villa-Collar. 2021. "The Influence of Genetics in Myopia Control: A Pilot Study" Journal of Clinical Medicine 10, no. 4: 808. https://doi.org/10.3390/jcm10040808