Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia
As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = −0.16 mm per minor allele, Pmeta = 2.69×10−10). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68–0.84, Pmeta = 4.38×10−7) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.
Vyšlo v časopise:
Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia. PLoS Genet 8(6): e32767. doi:10.1371/journal.pgen.1002753
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002753
Souhrn
As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = −0.16 mm per minor allele, Pmeta = 2.69×10−10). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68–0.84, Pmeta = 4.38×10−7) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.
Zdroje
1. PanCWRamamurthyDSawSM 2012 Worldwide prevalence and risk factors for myopia. Ophthalmic Physiol Opt 32 3 16
2. SawSMChuaWHGazzardGKohDTanDT 2005 Eye growth changes in myopic children in Singapore. Br J Ophthalmol 89 1489 1494
3. WongTYFosterPJHeeJNgTPTielschJM 2000 Prevalence and risk factors for refractive errors in adult Chinese in Singapore. Invest Ophthalmol Vis Sci 41 2486 2494
4. SawSMGazzardGShih-YenECChuaWH 2005 Myopia and associated pathological complications. Ophthalmic Physiol Opt 25 381 391
5. McBrienNAGentleA 2003 Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res 22 307 338
6. SawSMKatzJScheinODChewSJChanTK 1996 Epidemiology of myopia. Epidemiol Rev 18 175 187
7. HammondCJSniederHGilbertCESpectorTD 2001 Genes and environment in refractive error: the twin eye study. Invest Ophthalmol Vis Sci 42 1232 1236
8. KleinAPSuktitipatBDuggalPLeeKEKleinR 2009 Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study. Arch Ophthalmol 127 649 655
9. LyhneNSjolieAKKyvikKOGreenA 2001 The importance of genes and environment for ocular refraction and its determiners: a population based study among 20–45 year old twins. Br J Ophthalmol 85 1470 1476
10. SanfilippoPGHewittAWHammondCJMackeyDA 2010 The heritability of ocular traits. Surv Ophthalmol 55 561 583
11. SoloukiAMVerhoevenVJvan DuijnCMVerkerkAJIkramMK 2010 A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet 42 897 901
12. HysiPGYoungTLMackeyDAAndrewTFernandez-MedardeA 2010 A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25. Nat Genet 42 902 905
13. NakanishiHYamadaRGotohNHayashiHYamashiroK 2009 A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1. PLoS Genet 5 e1000660 doi:10.1371/journal.pgen.1000660
14. LiYJGohLKhorCCFanQYuM 2011 Genome-wide association studies reveal genetic variants in CTNND2 for high myopia in Singapore Chinese. Ophthalmology 118 368 375
15. LiZQuJXuXZhouXZouH 2011 A genome-wide association study reveals association between common variants in an intergenic region of 4q25 and high-grade myopia in the Chinese Han population. Hum Mol Genet 20 2861 2868
16. ShiYQuJZhangDZhaoPZhangQ 2011 Genetic variants at 13q12.12 are associated with high myopia in the han chinese population. Am J Hum Genet 88 805 813
17. SawSMShankarATanSBTaylorHTanDT 2006 A cohort study of incident myopia in Singaporean children. Invest Ophthalmol Vis Sci 47 1839 1844
18. DiraniMShekarSNBairdPN 2008 Evidence of shared genes in refraction and axial length: the Genes in Myopia (GEM) twin study. Invest Ophthalmol Vis Sci 49 4336 4339
19. BiinoGPalmasMACoronaCProdiDFanciulliM 2005 Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population. Hum Genet 116 152 159
20. ZhuGHewittAWRuddleJBKearnsLSBrownSA 2008 Genetic dissection of myopia: evidence for linkage of ocular axial length to chromosome 5q. Ophthalmology 115 1053 1057 e1052
21. LeungKWLiuMXuXSeilerMJBarnstableCJ 2008 Expression of ZnT and ZIP zinc transporters in the human RPE and their regulation by neurotrophic factors. Invest Ophthalmol Vis Sci 49 1221 1231
22. LiangJSongWTrompGKolattukudyPEFuM 2008 Genome-wide survey and expression profiling of CCCH-zinc finger family reveals a functional module in macrophage activation. PLoS ONE 3 e2880 doi:10.1371/journal.pone.0002880
23. PolisenoLSalmenaLZhangJCarverBHavemanWJ 2010 A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465 1033 1038
24. SalmenaLPolisenoLTayYKatsLPandolfiPP 2011 A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? Cell 146 353 358
25. D'ErricoIGadaletaGSacconeC 2004 Pseudogenes in metazoa: origin and features. Brief Funct Genomic Proteomic 3 157 167
26. ShiYLiYZhangDZhangHLuF 2011 Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet 7 e1002084 doi:10.1371/journal.pgen.1002084
27. SchippertRBurkhardtEFeldkaemperMSchaeffelF 2007 Relative axial myopia in Egr-1 (ZENK) knockout mice. Invest Ophthalmol Vis Sci 48 11 17
28. LaityJHLeeBMWrightPE 2001 Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11 39 46
29. FischerAJMcGuireJJSchaeffelFStellWK 1999 Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Nat Neurosci 2 706 712
30. BitzerMSchaeffelF 2002 Defocus-induced changes in ZENK expression in the chicken retina. Invest Ophthalmol Vis Sci 43 246 252
31. SimonPFeldkaemperMBitzerMOhngemachSSchaeffelF 2004 Early transcriptional changes of retinal and choroidal TGFbeta-2, RALDH-2, and ZENK following imposed positive and negative defocus in chickens. Mol Vis 10 588 597
32. LiuCAdamsonEMercolaD 1996 Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1. Proc Natl Acad Sci U S A 93 11831 11836
33. BaronVAdamsonEDCalogeroARagonaGMercolaD 2006 The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther 13 115 124
34. KhorCCFanQGohLTanDYoungTL 2010 Support for TGFB1 as a susceptibility gene for high myopia in individuals of Chinese descent. Arch Ophthalmol 128 1081 1084
35. ZhaYLeungKHLoKKFungWYNgPW 2009 TGFB1 as a susceptibility gene for high myopia: a replication study with new findings. Arch Ophthalmol 127 541 548
36. SeveMChimientiFDevergnasSFavierA 2004 In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression. BMC Genomics 5 32
37. van LeeuwenRBoekhoornSVingerlingJRWittemanJCKlaverCC 2005 Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 294 3101 3107
38. UgarteMOsborneNN 2001 Zinc in the retina. Prog Neurobiol 64 219 249
39. HuibiXKaixunHQiuhuaGYushanZXiuxianH 2001 Prevention of axial elongation in myopia by the trace element zinc. Biol Trace Elem Res 79 39 47
40. SteinbergGRKempBEWattMJ 2007 Adipocyte triglyceride lipase expression in human obesity. Am J Physiol Endocrinol Metab 293 E958 964
41. HeidIMJacksonAURandallJCWinklerTWQiL 2010 Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 42 949 960
42. LindgrenCMHeidIMRandallJCLaminaCSteinthorsdottirV 2009 Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet 5 e1000508 doi:10.1371/journal.pgen.1000508
43. CordainLEatonSBBrand MillerJLindebergSJensenC 2002 An evolutionary analysis of the aetiology and pathogenesis of juvenile-onset myopia. Acta Ophthalmol Scand 80 125 135
44. CordainLEadesMREadesMD 2003 Hyperinsulinemic diseases of civilization: more than just Syndrome X. Comp Biochem Physiol A Mol Integr Physiol 136 95 112
45. LimLSGazzardGLowYLChooRTanDT 2010 Dietary factors, myopia, and axial dimensions in children. Ophthalmology 117 993 997 e994
46. GaoHFrostMRSiegwartJTJrNortonTT 2011 Patterns of mRNA and protein expression during minus-lens compensation and recovery in tree shrew sclera. Mol Vis 17 903 919
47. KleinAPDuggalPLeeKEKleinRBailey-WilsonJE 2007 Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q. Arch Ophthalmol 125 80 85
48. KleinAPDuggalPLeeKEChengCYKleinR 2011 Linkage analysis of quantitative refraction and refractive errors in the beaver dam eye study. Invest Ophthalmol Vis Sci 52 5220 5225
49. WongTYFosterPJJohnsonGJSeahSK 2003 Refractive errors, axial ocular dimensions, and age-related cataracts: the Tanjong Pagar survey. Invest Ophthalmol Vis Sci 44 1479 1485
50. WuRWangJJMitchellPLamoureuxELZhengY 2010 Smoking, socioeconomic factors, and age-related cataract: The Singapore Malay Eye study. Arch Ophthalmol 128 1029 1035
51. TokoroT 1988 On the definition of pathologic myopia in group studies. Acta Ophthalmol Suppl 185 107 108
52. PlominRHaworthCMDavisOS 2009 Common disorders are quantitative traits. Nat Rev Genet 10 872 878
53. HayashiHYamashiroKNakanishiHNakataIKurashigeY 2011 Association of 15q14 and 15q25 with High Myopia in Japanese. Invest Ophthalmol Vis Sci
54. DiraniMShekarSNBairdPN 2008 Adult-onset myopia: the Genes in Myopia (GEM) twin study. Invest Ophthalmol Vis Sci 49 3324 3327
55. JensenH 1995 Myopia in teenagers. An eight-year follow-up study on myopia progression and risk factors. Acta Ophthalmol Scand 73 389 393
56. McCarthyMIHirschhornJN 2008 Genome-wide association studies: potential next steps on a genetic journey. Hum Mol Genet 17 R156 165
57. TeoYYSmallKSFryAEWuYKwiatkowskiDP 2009 Power consequences of linkage disequilibrium variation between populations. Genet Epidemiol 33 128 135
58. IpJMHuynhSCKifleyARoseKAMorganIG 2007 Variation of the contribution from axial length and other oculometric parameters to refraction by age and ethnicity. Invest Ophthalmol Vis Sci 48 4846 4853
59. LavanyaRJeganathanVSZhengYRajuPCheungN 2009 Methodology of the Singapore Indian Chinese Cohort (SICC) eye study: quantifying ethnic variations in the epidemiology of eye diseases in Asians. Ophthalmic Epidemiol 16 325 336
60. FanQZhouXKhorCCChengCYGohLK 2011 Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for corneal astigmatism. PLoS Genet 7 e1002402 doi:10.1371/journal.pgen.1002402
61. FoongAWSawSMLooJLShenSLoonSC 2007 Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay eye study (SiMES). Ophthalmic Epidemiol 14 25 35
62. VithanaENAungTKhorCCCornesBKTayWT 2011 Collagen-related genes influence the glaucoma risk factor, central corneal thickness. Hum Mol Genet 20 649 658
63. KhorCCRamdasWDVithanaENCornesBKSimX 2011 Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area. Hum Mol Genet 20 1864 1872
64. GrosvenorTP 2007 Primary care optometry St. Louis, Mo Butterworth-Heinemann/Elsevier xiii, 510 p.
65. SchorkNJNathSKFallinDChakravartiA 2000 Linkage disequilibrium analysis of biallelic DNA markers, human quantitative trait loci, and threshold-defined case and control subjects. Am J Hum Genet 67 1208 1218
66. SawSMChanYHWongWLShankarASandarM 2008 Prevalence and risk factors for refractive errors in the Singapore Malay Eye Survey. Ophthalmology 115 1713 1719
67. FanDSLamDSLamRFLauJTChongKS 2004 Prevalence, incidence, and progression of myopia of school children in Hong Kong. Invest Ophthalmol Vis Sci 45 1071 1075
68. SimXOngRTSuoCTayWTLiuJ 2011 Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet 7 e1001363 doi:10.1371/journal.pgen.1001363
69. PurcellSNealeBTodd-BrownKThomasLFerreiraMA 2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575
70. AndersonCAPetterssonFHClarkeGMCardonLRMorrisAP 2010 Data quality control in genetic case-control association studies. Nat Protoc 5 1564 1573
71. PriceALPattersonNJPlengeRMWeinblattMEShadickNA 2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909
72. SchaeffelFBurkhardtEHowlandHCWilliamsRW 2004 Measurement of refractive state and deprivation myopia in two strains of mice. Optom Vis Sci 81 99 110
73. BarathiVABoopathiVGYapEPBeuermanRW 2008 Two models of experimental myopia in the mouse. Vision Res 48 904 916
74. RozenSSkaletskyH 2000 Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132 365 386
75. FanQTeoYYSawSM 2011 Application of advanced statistics in ophthalmology. Invest Ophthalmol Vis Sci 52 6059 6065
76. BrinkNSzamelMYoungARWitternKPBergemannJ 2000 Comparative quantification of IL-1beta, IL-10, IL-10r, TNFalpha and IL-7 mRNA levels in UV-irradiated human skin in vivo. Inflamm Res 49 290 296
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 6
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Rumors of Its Disassembly Have Been Greatly Exaggerated: The Secret Life of the Synaptonemal Complex at the Centromeres
- The NSL Complex Regulates Housekeeping Genes in
- Tipping the Balance in the Powerhouse of the Cell to “Protect” Colorectal Cancer
- Interplay between Synaptonemal Complex, Homologous Recombination, and Centromeres during Mammalian Meiosis