1932

Abstract

Glaucoma is a clinically heterogeneous disease and the world's leading cause of irreversible blindness. Therapeutic intervention can prevent blindness but relies on early diagnosis, and current clinical risk factors are limited in their ability to predict who will develop sight-threatening glaucoma. The high heritability of glaucoma makes it an ideal substrate for genetic risk prediction, with the bulk of risk being polygenic in nature. Here, we summarize the foundations of glaucoma genetic risk, the development of polygenic risk prediction instruments, and emerging opportunities for genetic risk stratification. Although challenges remain, genetic risk stratification will significantly improve glaucoma screening and management.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-121222-105817
2024-08-27
2025-02-09
Loading full text...

Full text loading...

/deliver/fulltext/genom/25/1/annurev-genom-121222-105817.html?itemId=/content/journals/10.1146/annurev-genom-121222-105817&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Adam MF, Belmouden A, Binisti P, Brézin AP, Valtot F, et al. 1997.. Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. . Hum. Mol. Genet. 6:(12):209197
    [Crossref] [Google Scholar]
  2. 2.
    Alipanahi B, Hormozdiari F, Behsaz B, Cosentino J, McCaw ZR, et al. 2021.. Large-scale machine-learning-based phenotyping significantly improves genomic discovery for optic nerve head morphology. . Am. J. Hum. Genet. 108:(7):121730
    [Crossref] [Google Scholar]
  3. 3.
    Anderson DR. 2003.. Collaborative Normal Tension Glaucoma Study. . Curr. Opin. Ophthalmol. 14:(2):8690
    [Crossref] [Google Scholar]
  4. 4.
    Ayoub A, Lapointe J, Nabi H, Pashayan N. 2023.. Risk-stratified breast cancer screening incorporating a polygenic risk score: a survey of UK general practitioners’ knowledge and attitudes. . Genes 14:(3):732
    [Crossref] [Google Scholar]
  5. 5.
    Bailey JNC, Loomis SJ, Kang JH, Allingham RR, Gharahkhani P, et al. 2016.. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. . Nat. Genet. 48:(2):18994
    [Crossref] [Google Scholar]
  6. 6.
    Baird PN, Craig JE, Richardson AJ, Ring MA, Sim P, et al. 2003.. Analysis of 15 primary open-angle glaucoma families from Australia identifies a founder effect for the Q368STOP mutation of myocilin. . Hum. Genet. 112:(2):11016
    [Crossref] [Google Scholar]
  7. 7.
    Burdon KP, Graham P, Hadler J, Hulleman JD, Pasutto F, et al. 2022.. Specifications of the ACMG/AMP variant curation guidelines for myocilin: recommendations from the ClinGen Glaucoma Expert Panel. . Hum. Mutat. 43:(12):217086
    [Crossref] [Google Scholar]
  8. 8.
    Burdon KP, Macgregor S, Hewitt AW, Sharma S, Chidlow G, et al. 2011.. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. . Nat. Genet. 43:(6):57478
    [Crossref] [Google Scholar]
  9. 9.
    Burr JM, Mowatt G, Hernández R, Siddiqui MAR, Cook J, et al. 2007.. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. . Health Technol. Assess. 11:(41):1190
    [Crossref] [Google Scholar]
  10. 10.
    Bussel II, Wollstein G, Schuman JS. 2014.. OCT for glaucoma diagnosis, screening and detection of glaucoma progression. . Br. J. Ophthalmol. 98:(Suppl. 2):ii1519
    [Crossref] [Google Scholar]
  11. 11.
    Chen Y, Lin Y, Vithana EN, Jia L, Zuo X, et al. 2014.. Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma. . Nat. Genet. 46:(10):111519
    [Crossref] [Google Scholar]
  12. 12.
    Choquet H, Thai KK, Yin J, Hoffmann TJ, Kvale MN, et al. 2017.. A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure. . Nat. Commun. 8::2108
    [Crossref] [Google Scholar]
  13. 13.
    Chou R, Selph S, Blazina I, Bougatsos C, Jungbauer R, et al. 2022.. Screening for glaucoma in adults: updated evidence report and systematic review for the US Preventive Services Task Force. . JAMA 327:(20):19982012
    [Crossref] [Google Scholar]
  14. 14.
    Chrysostomou V, Rezania F, Trounce IA, Crowston JG. 2013.. Oxidative stress and mitochondrial dysfunction in glaucoma. . Curr. Opin. Pharmacol. 13:(1):1215
    [Crossref] [Google Scholar]
  15. 15.
    Clin. Genome Resour. 2023.. Glaucoma and Neuro-Ophthalmology Expert Panel. . Clinical Genome Resource. https://search.clinicalgenome.org/kb/affiliate/10077
    [Google Scholar]
  16. 16.
    Cole BS, Gudiseva HV, Pistilli M, Salowe R, McHugh CP, et al. 2021.. The role of genetic ancestry as a risk factor for primary open-angle glaucoma in African Americans. . Investig. Ophthalmol. Vis. Sci. 62:(2):28
    [Crossref] [Google Scholar]
  17. 17.
    Cooke Bailey JN, Funk KL, Cruz LA, Waksmunski AR, Kinzy TG, et al. 2022.. Diversity in polygenic risk of primary open-angle glaucoma. . Genes 14:(1):111
    [Crossref] [Google Scholar]
  18. 18.
    Craig JE, Baird PN, Healey DL, McNaught AI, McCartney PJ, et al. 2001.. Evidence for genetic heterogeneity within eight glaucoma families, with the GLC1A Gln368STOP mutation being an important phenotypic modifier. . Ophthalmology 108:(9):160720
    [Crossref] [Google Scholar]
  19. 19.
    Craig JE, Han X, Qassim A, Hassall M, Cooke Bailey JN, et al. 2020.. Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression. . Nat. Genet. 52:(2):16066
    [Crossref] [Google Scholar]
  20. 20.
    Cupido AJ, Tromp TR, Hovingh GK. 2021.. The clinical applicability of polygenic risk scores for LDL-cholesterol: considerations, current evidence and future perspectives. . Curr. Opin. Lipidol. 32:(2):11216
    [Crossref] [Google Scholar]
  21. 21.
    Damask A, Steg PG, Schwartz GG, Szarek M, Hagström E, et al. 2020.. Patients with high genome-wide polygenic risk scores for coronary artery disease may receive greater clinical benefit from alirocumab treatment in the ODYSSEY OUTCOMES trial. . Circulation 141:(8):62436
    [Crossref] [Google Scholar]
  22. 22.
    Danford ID, Verkuil LD, Choi DJ, Collins DW, Gudiseva HV, et al. 2017.. Characterizing the “POAGome”: a bioinformatics-driven approach to primary open-angle glaucoma. . Prog. Retin. Eye Res. 58::89114
    [Crossref] [Google Scholar]
  23. 23.
    de Vries VA, Hanyuda A, Vergroesen J, Do R, Friedman DS, et al. 2023.. The clinical utility of a glaucoma polygenic risk score in four European-ancestry cohorts. . Investig. Ophthalmol. Vis. Sci. 64:(8):99
    [Google Scholar]
  24. 24.
    Diehl DL, Quigley HA, Miller NR, Sommer A, Burney EN. 1990.. Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma. . Arch. Ophthalmol. 108:(4):54550
    [Crossref] [Google Scholar]
  25. 25.
    Duncan L, Shen H, Gelaye B, Meijsen J, Ressler K, et al. 2019.. Analysis of polygenic risk score usage and performance in diverse human populations. . Nat. Commun. 10::3328
    [Crossref] [Google Scholar]
  26. 26.
    Fan BJ, Bailey JC, Igo RP Jr., Kang JH, Boumenna T, et al. 2019.. Association of a primary open-angle glaucoma genetic risk score with earlier age at diagnosis. . JAMA Ophthalmol. 137:(10):119094
    [Crossref] [Google Scholar]
  27. 27.
    Financ. Serv. Counc. 2019.. FSC Standard No. 11: moratorium on genetic tests in life insurance. Stand. Doc., Financ. Serv. Counc., Sydney:. https://www.fsc.org.au/resources-category/standard/1779-standard-11-moratorium-on-genetic-tests-in-life-insurance/file
    [Google Scholar]
  28. 28.
    Fingert JH, Héon E, Liebmann JM, Yamamoto T, Craig JE, et al. 1999.. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. . Hum. Mol. Genet. 8:(5):899905
    [Crossref] [Google Scholar]
  29. 29.
    Fingert JH, Robin AL, Stone JL, Roos BR, Davis LK, et al. 2011.. Copy number variations on chromosome 12q14 in patients with normal tension glaucoma. . Hum. Mol. Genet. 20:(12):248294
    [Crossref] [Google Scholar]
  30. 30.
    Fingert JH, Ying L, Swiderski RE, Nystuen AM, Arbour NC, et al. 1998.. Characterization and comparison of the human and mouse GLC1A glaucoma genes. . Genome Res. 8:(4):37784
    [Crossref] [Google Scholar]
  31. 31.
    Forrest LE, Sawyer SD, Hallowell N, James PA, Young M-A. 2019.. High-risk women's risk perception after receiving personalized polygenic breast cancer risk information. . J. Community Genet. 10:(2):197206
    [Crossref] [Google Scholar]
  32. 32.
    Gallagher S, Hughes E, Wagner S, Tshiaba P, Rosenthal E, et al. 2020.. Association of a polygenic risk score with breast cancer among women carriers of high- and moderate-risk breast cancer genes. . JAMA Netw. Open. 3:(7):e208501
    [Crossref] [Google Scholar]
  33. 33.
    Gao XR, Huang H, Kim H. 2019.. Polygenic risk score is associated with intraocular pressure and improves glaucoma prediction in the UK Biobank cohort. . Transl. Vis. Sci. Technol. 8:(2):10
    [Crossref] [Google Scholar]
  34. 34.
    Gao XR, Huang H, Nannini DR, Fan F, Kim H. 2018.. Genome-wide association analyses identify new loci influencing intraocular pressure. . Hum. Mol. Genet. 27:(12):220513
    [Crossref] [Google Scholar]
  35. 35.
    Garway-Heath DF, Crabb DP, Bunce C, Lascaratos G, Amalfitano F, et al. 2015.. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. . Lancet 385:(9975):1295304
    [Crossref] [Google Scholar]
  36. 36.
    Gazzard G, Konstantakopoulou E, Garway-Heath D, Garg A, Vickerstaff V, et al. 2019.. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. . Lancet 393:(10180):150516
    [Crossref] [Google Scholar]
  37. 37.
    Gedde SJ, Vinod K, Wright MM, Muir KW, Lind JT, et al. 2021.. Primary open-angle glaucoma Preferred Practice Pattern®. . Ophthalmology 128:(1):P71150
    [Crossref] [Google Scholar]
  38. 38.
    Gharahkhani P, Burdon KP, Fogarty R, Sharma S, Hewitt AW, et al. 2014.. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. . Nat. Genet. 46:(10):112025
    [Crossref] [Google Scholar]
  39. 39.
    Gharahkhani P, Burdon KP, Hewitt AW, Law MH, Souzeau E, et al. 2015.. Accurate imputation-based screening of Gln368Ter myocilin variant in primary open-angle glaucoma. . Investig. Ophthalmol. Vis. Sci. 56:(9):508793
    [Crossref] [Google Scholar]
  40. 40.
    Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, et al. 2021.. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. . Nat. Commun. 12::1258
    [Crossref] [Google Scholar]
  41. 41.
    Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, et al. 2002.. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. . Arch. Ophthalmol. 120:(6):71420
    [Crossref] [Google Scholar]
  42. 42.
    Green ML, Klein TE. 2002.. A multidomain TIGR/olfactomedin protein family with conserved structural similarity in the N-terminal region and conserved motifs in the C-terminal region. . Mol. Cell. Proteom. 1:(5):394403
    [Crossref] [Google Scholar]
  43. 43.
    Han X, Gharahkhani P, Hamel AR, Ong JS, Rentería ME, et al. 2023.. Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci. . Nat. Genet. 55:(7):111625
    [Crossref] [Google Scholar]
  44. 44.
    Han X, Hewitt AW, MacGregor S. 2021.. Predicting the future of genetic risk profiling of glaucoma: a narrative review. . JAMA Ophthalmol. 139:(2):22431
    [Crossref] [Google Scholar]
  45. 45.
    Han X, Souzeau E, Ong J-S, An J, Siggs OM, et al. 2019.. Myocilin gene Gln368Ter variant penetrance and association with glaucoma in population-based and registry-based studies. . JAMA Ophthalmol. 137:(1):2835
    [Crossref] [Google Scholar]
  46. 46.
    Han X, Steven K, Qassim A, Marshall HN, Bean C, et al. 2021.. Automated AI labeling of optic nerve head enables insights into cross-ancestry glaucoma risk and genetic discovery in >280,000 images from UKB and CLSA. . Am. J. Hum. Genet. 108:(7):120416
    [Crossref] [Google Scholar]
  47. 47.
    Hewitt AW, Mackey DA, Craig JE. 2008.. Myocilin allele-specific glaucoma phenotype database. . Hum. Mutat. 29:(2):20711
    [Crossref] [Google Scholar]
  48. 48.
    Hollitt GL, Siggs OM, Ridge B, Keane MC, Mackey DA, et al. 2022.. Attitudes toward glaucoma genetic risk assessment in unaffected individuals. . Transl. Vis. Sci. Technol. 11:(10):38
    [Crossref] [Google Scholar]
  49. 49.
    Hollitt GL, Siggs OM, Ridge B, Keane MC, Mackey DA, et al. 2022.. Attitudes towards polygenic risk testing in individuals with glaucoma. . Ophthalmol. Glaucoma 5:(4):43646
    [Crossref] [Google Scholar]
  50. 50.
    Hsiao Y-J, Chuang H-K, Chi S-C, Wang Y-Y, Chiang P-H, et al. 2021.. Genome-wide polygenic risk score for predicting high risk glaucoma individuals of Han Chinese ancestry. . J. Pers. Med. 11:(11):1169
    [Crossref] [Google Scholar]
  51. 51.
    Hughes E, Tshiaba P, Wagner S, Judkins T, Rosenthal E, et al. 2021.. Integrating clinical and polygenic factors to predict breast cancer risk in women undergoing genetic testing. . JCO Precis Oncol. 5::PO.20.00246
    [Google Scholar]
  52. 52.
    Hysi PG, Cheng C-Y, Springelkamp H, Macgregor S, Bailey JNC, et al. 2014.. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. . Nat. Genet. 46:(10):112630
    [Crossref] [Google Scholar]
  53. 53.
    Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, et al. 2018.. Genomic risk prediction of coronary artery disease in 480,000 adults: implications for primary prevention. . J. Am. Coll. Cardiol. 72:(16):188393
    [Crossref] [Google Scholar]
  54. 54.
    Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, et al. 2002.. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. . Arch. Ophthal. 120:(6):70113
    [Crossref] [Google Scholar]
  55. 55.
    Kass MA, Heuer DK, Higginbotham EJ, Parrish RK, Khanna CL, et al. 2021.. Assessment of cumulative incidence and severity of primary open-angle glaucoma among participants in the ocular hypertension treatment study after 20 years of follow-up. . JAMA Ophthalmol. 139:(5):55866
    [Crossref] [Google Scholar]
  56. 56.
    Khawaja AP, Cooke Bailey JN, Wareham NJ, Scott RA, Simcoe M, et al. 2018.. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. . Nat. Genet. 50:(6):77882
    [Crossref] [Google Scholar]
  57. 57.
    Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, et al. 2018.. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. . Nat. Genet. 50:(9):121924
    [Crossref] [Google Scholar]
  58. 58.
    Lambert SA, Gil L, Jupp S, Ritchie SC, Xu Y, et al. 2021.. The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation. . Nat. Genet. 53:(4):42025
    [Crossref] [Google Scholar]
  59. 59.
    Lapointe J, Buron A-C, Mbuya-Bienge C, Dorval M, Pashayan N, et al. 2022.. Polygenic risk scores and risk-stratified breast cancer screening: familiarity and perspectives of health care professionals. . Genet. Med. 24:(11):238088
    [Crossref] [Google Scholar]
  60. 60.
    Lee JWY, Chan PP, Zhang X, Chen LJ, Jonas JB. 2019.. Latest developments in normal-pressure glaucoma: diagnosis, epidemiology, genetics, etiology, causes and mechanisms to management. . Asia Pac. J. Ophthalmol. 8:(6):45768
    [Crossref] [Google Scholar]
  61. 61.
    Lee PP, Walt JG, Doyle JJ, Kotak SV, Evans SJ, et al. 2006.. A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glaucoma. . Arch. Ophthalmol. 124:(1):1219
    [Crossref] [Google Scholar]
  62. 62.
    Lee S, Van Bergen NJ, Kong GY, Chrysostomou V, Waugh HS, et al. 2011.. Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies. . Exp. Eye Res. 93:(2):20412
    [Crossref] [Google Scholar]
  63. 63.
    Leske MC, Connell AM, Wu SY, Hyman LG, Schachat AP. 1995.. Risk factors for open-angle glaucoma: the Barbados Eye Study. . Arch. Ophthalmol. 113:(7):91824
    [Crossref] [Google Scholar]
  64. 64.
    Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, et al. 2003.. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. . Arch. Ophthalmol. 121:(1):4856
    [Crossref] [Google Scholar]
  65. 65.
    Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, et al. 2007.. Predictors of long-term progression in the early manifest glaucoma trial. . Ophthalmology 114:(11):196572
    [Crossref] [Google Scholar]
  66. 66.
    Leske MC, Heijl A, Hyman L, Bengtsson B, Komaroff E. 2004.. Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial. . Curr. Opin. Ophthalmol. 15:(2):1026
    [Crossref] [Google Scholar]
  67. 67.
    Lichter PR, Musch DC, Janz NK. 2008.. The investigators’ perspective on the Collaborative Initial Glaucoma Treatment Study (CIGTS). . Arch. Ophthalmol. 126:(1):12224
    [Crossref] [Google Scholar]
  68. 68.
    Liu Q, Davis J, Han X, Mackey DA, MacGregor S, et al. 2023.. Cost-effectiveness of polygenic risk profiling for primary open-angle glaucoma in the United Kingdom and Australia. . Eye 37:(11):233543
    [Crossref] [Google Scholar]
  69. 69.
    Ludwig KK, Neuner J, Butler A, Geurts JL, Kong AL. 2016.. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. . Am. J. Surg. 212:(4):66069
    [Crossref] [Google Scholar]
  70. 70.
    MacGregor S, Ong J-S, An J, Han X, Zhou T, et al. 2018.. Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. . Nat. Genet. 50:(8):106771
    [Crossref] [Google Scholar]
  71. 71.
    Mackay DS, Bennett TM, Shiels A. 2015.. Exome sequencing identifies a missense variant in EFEMP1 co-segregating in a family with autosomal dominant primary open-angle glaucoma. . PLOS ONE 10:(7):e0132529
    [Crossref] [Google Scholar]
  72. 72.
    Mars N, Lindbohm JV, Della Briotta Parolo P, Widén E, Kaprio J, et al. 2022.. Systematic comparison of family history and polygenic risk across 24 common diseases. . Am. J. Hum. Genet. 109:(12):215262
    [Crossref] [Google Scholar]
  73. 73.
    Marshall HN, Hollitt GL, Wilckens K, Mullany S, Kuruvilla S, et al. 2023.. High polygenic risk is associated with earlier trabeculectomy in patients with primary open-angle glaucoma. . Ophthalmol. Glaucoma 6:(1):5457
    [Crossref] [Google Scholar]
  74. 74.
    Marshall HN, Mullany S, Han X, Qassim A, He W, et al. 2023.. High polygenic risk is associated with earlier initiation and escalation of treatment in early primary open-angle glaucoma. . Ophthalmology 130:(8):83036
    [Crossref] [Google Scholar]
  75. 75.
    Marshall HN, Mullany S, Qassim A, Siggs O, Hassall M, et al. 2021.. Cardiovascular disease predicts structural and functional progression in early glaucoma. . Ophthalmology 128:(1):5869
    [Crossref] [Google Scholar]
  76. 76.
    Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ. 2019.. Clinical use of current polygenic risk scores may exacerbate health disparities. . Nat. Genet. 51:(4):58491
    [Crossref] [Google Scholar]
  77. 77.
    McGuinness M, Fassi E, Wang C, Hacking C, Ellis V. 2021.. Breast cancer polygenic risk scores in the clinical cancer genetic counseling setting: current practices and impact on patient management. . J. Genet. Couns. 30:(2):58897
    [Crossref] [Google Scholar]
  78. 78.
    McNaught AI, Allen JG, Healey DL, McCartney PJ, Coote MA, et al. 2000.. Accuracy and implications of a reported family history of glaucoma: experience from the Glaucoma Inheritance Study in Tasmania. . Arch. Ophthalmol. 118:(7):9004
    [Google Scholar]
  79. 79.
    Mitchell P, Rochtchina E, Lee AJ, Wang JJ. 2002.. Bias in self-reported family history and relationship to glaucoma: the Blue Mountains Eye Study. . Ophthalmic Epidemiol. 9:(5):33345
    [Crossref] [Google Scholar]
  80. 80.
    Mitchell P, Smith W, Attebo K, Healey PR. 1996.. Prevalence of open-angle glaucoma in Australia: the Blue Mountains Eye Study. . Ophthalmology 103:(10):166169
    [Crossref] [Google Scholar]
  81. 81.
    Nag A, Lu H, Arno M, Iglesias AI, Bonnemaijer P, et al. 2017.. Evaluation of the myocilin mutation Gln368Stop demonstrates reduced penetrance for glaucoma in European populations. . Ophthalmology 124:(4):54753
    [Crossref] [Google Scholar]
  82. 82.
    Nannini DR, Torres M, Chen Y-DI, Taylor KD, Rotter JI, et al. 2017.. A genome-wide association study of vertical cup-disc ratio in a Latino population. . Investig. Ophthalmol. Vis. Sci. 58:(1):8795
    [Crossref] [Google Scholar]
  83. 83.
    Nelson MR, Tipney H, Painter JL, Shen J, Nicoletti P, et al. 2015.. The support of human genetic evidence for approved drug indications. . Nat. Genet. 47:(8):85660
    [Crossref] [Google Scholar]
  84. 84.
    Nouri-Mahdavi K, Hoffman D, Coleman AL, Liu G, Li G, et al. 2004.. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. . Ophthalmology 111:(9):162735
    [Crossref] [Google Scholar]
  85. 85.
    O'Neill EC, Gurria LU, Pandav SS, Kong YXG, Brennan JF, et al. 2014.. Glaucomatous optic neuropathy evaluation project: factors associated with underestimation of glaucoma likelihood. . JAMA Ophthalmol. 132:(5):56066
    [Crossref] [Google Scholar]
  86. 86.
    O'Sullivan JW, Raghavan S, Marquez-Luna C, Luzum JA, Damrauer SM, et al. 2022.. Polygenic risk scores for cardiovascular disease: a scientific statement from the American Heart Association. . Circulation 146:(8):e93118
    [Google Scholar]
  87. 87.
    O'Sullivan JW, Shcherbina A, Justesen JM, Turakhia M, Perez M, et al. 2021.. Combining clinical and polygenic risk improves stroke prediction among individuals with atrial fibrillation. . Circ. Genom. Precis. Med. 14:(3):e003168
    [Crossref] [Google Scholar]
  88. 88.
    Pan Y, Suga A, Kimura I, Kimura C, Minegishi Y, et al. 2022.. METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma. . J. Clin. Investig. 132:(21):e153589
    [Crossref] [Google Scholar]
  89. 89.
    PanelApp. 2023.. Glaucoma (developmental) (version 1.42). . PanelApp. https://panelapp.genomicsengland.co.uk/panels/249
    [Google Scholar]
  90. 90.
    Parkman AA, Foland J, Anderson B, Duquette D, Sobotka H, et al. 2015.. Public awareness of genetic nondiscrimination laws in four states and perceived importance of life insurance protections. . J. Genet. Couns. 24:(3):51221
    [Crossref] [Google Scholar]
  91. 91.
    Peters D, Bengtsson B, Heijl A. 2013.. Lifetime risk of blindness in open-angle glaucoma. . Am. J. Ophthalmol. 156:(4):72430
    [Crossref] [Google Scholar]
  92. 92.
    Phu J, Masselos K, Sullivan-Mee M, Kalloniatis M. 2022.. Glaucoma suspects: the impact of risk factor-driven review periods on clinical load, diagnoses, and healthcare costs. . Transl. Vis. Sci. Technol. 11:(1):37
    [Crossref] [Google Scholar]
  93. 93.
    Qassim A, Mullany S, Abedi F, Marshall H, Hassall MM, et al. 2020.. Corneal stiffness parameters are predictive of structural and functional progression in glaucoma suspect eyes. . Ophthalmology 128:(7):9931004
    [Crossref] [Google Scholar]
  94. 94.
    Qassim A, Mullany S, Awadalla MS, Hassall MM, Nguyen T, et al. 2021.. A polygenic risk score predicts intraocular pressure readings outside office hours and early morning spikes as measured by home tonometry. . Ophthalmol. Glaucoma 4:(4):41120
    [Crossref] [Google Scholar]
  95. 95.
    Qassim A, Souzeau E, Siggs OM, Hassall MM, Han X, et al. 2020.. An intraocular pressure polygenic risk score stratifies multiple primary open-angle glaucoma parameters including treatment intensity. . Ophthalmology 127:(7):9017
    [Crossref] [Google Scholar]
  96. 96.
    Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. 1983.. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. . Am. J. Ophthalmol. 95:(5):67391
    [Crossref] [Google Scholar]
  97. 97.
    Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. 1995.. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. . Investig. Ophthalmol. Vis. Sci. 36:(5):77486
    [Google Scholar]
  98. 98.
    Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. 2001.. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. . Arch. Ophthalmol. 119:(12):181926
    [Crossref] [Google Scholar]
  99. 99.
    Ramdas WD, van Koolwijk LME, Ikram MK, Jansonius NM, de Jong PTVM, et al. 2010.. A genome-wide association study of optic disc parameters. . PLOS Genet. 6:(6):e1000978
    [Crossref] [Google Scholar]
  100. 100.
    Ramdas WD, van Koolwijk LME, Lemij HG, Pasutto F, Cree AJ, et al. 2011.. Common genetic variants associated with open-angle glaucoma. . Hum. Mol. Genet. 20:(12):246471
    [Crossref] [Google Scholar]
  101. 101.
    Ramdas WD, Wolfs RCW, Kiefte-de Jong JC, Hofman A, de Jong PTVM, et al. 2012.. Nutrient intake and risk of open-angle glaucoma: the Rotterdam Study. . Eur. J. Epidemiol. 27:(5):38593
    [Crossref] [Google Scholar]
  102. 102.
    Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, et al. 2006.. The economic burden of major adult visual disorders in the United States. . Arch. Ophthalmol. 124:(12):175460
    [Crossref] [Google Scholar]
  103. 103.
    Rezaie T, Child A, Hitchings R, Brice G, Miller L, et al. 2002.. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. . Science 295:(5557):107779
    [Crossref] [Google Scholar]
  104. 104.
    Rotchford AP, Kirwan JF, Muller MA, Johnson GJ, Roux P. 2003.. Temba glaucoma study: a population-based cross-sectional survey in urban South Africa. . Ophthalmology 110:(2):37682
    [Crossref] [Google Scholar]
  105. 105.
    Sanfilippo PG, Hewitt AW, Hammond CJ, Mackey DA. 2010.. The heritability of ocular traits. . Surv. Ophthalmol. 55:(6):56183
    [Crossref] [Google Scholar]
  106. 106.
    Sears NC, Boese EA, Miller MA, Fingert JH. 2019.. Mendelian genes in primary open angle glaucoma. . Exp. Eye Res. 186::107702
    [Crossref] [Google Scholar]
  107. 107.
    Sengupta D, Botha G, Meintjes A, Mbiyavanga M, AWI-Gen Study, et al. 2023.. Performance and accuracy evaluation of reference panels for genotype imputation in sub-Saharan African populations. . Cell Genom. 3:(6):100332
    [Crossref] [Google Scholar]
  108. 108.
    Siggs OM, Han X, Qassim A, Souzeau E, Kuruvilla S, et al. 2021.. Association of monogenic and polygenic risk with the prevalence of open-angle glaucoma. . JAMA Ophthalmol. 139:(9):102328
    [Crossref] [Google Scholar]
  109. 109.
    Siggs OM, Qassim A, Han X, Marshall HN, Mullany S, et al. 2022.. Association of high polygenic risk with visual field worsening despite treatment in early primary open-angle glaucoma. . JAMA Ophthalmol. 141:(1):7377
    [Crossref] [Google Scholar]
  110. 110.
    Singh RK, Zhao Y, Elze T, Fingert J, Gordon M, et al. 2023.. Polygenic risk score improves prediction of primary open angle glaucoma onset in the ocular hypertension treatment study. . medRxiv 2023.08.15.23294141. https://doi.org/10.1101/2023.08.15.23294141
  111. 111.
    Smit AK, Sharman AR, Espinoza D, Wallingford C, Young M-A, et al. 2021.. Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals. . Clin. Genet. 100:(4):43039
    [Crossref] [Google Scholar]
  112. 112.
    Souzeau E, Burdon KP, Dubowsky A, Grist S, Usher B, et al. 2013.. Higher prevalence of myocilin mutations in advanced glaucoma in comparison with less advanced disease in an Australasian disease registry. . Ophthalmology 120:(6):113543
    [Crossref] [Google Scholar]
  113. 113.
    Souzeau E, Hayes M, Zhou T, Siggs OM, Ridge B, et al. 2015.. Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss. . JAMA Ophthalmol. 133:(7):82633
    [Crossref] [Google Scholar]
  114. 114.
    Souzeau E, Tram KH, Witney M, Ruddle JB, Graham SL, et al. 2017.. Myocilin predictive genetic testing for primary open-angle glaucoma leads to early identification of at-risk individuals. . Ophthalmology 124:(3):3039
    [Crossref] [Google Scholar]
  115. 115.
    Springelkamp H, Höhn R, Mishra A, Hysi PG, Khor C-C, et al. 2014.. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. . Nat. Commun. 5::4883
    [Crossref] [Google Scholar]
  116. 116.
    Springelkamp H, Iglesias AI, Mishra A, Höhn R, Wojciechowski R, et al. 2017.. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. . Hum. Mol. Genet. 26:(2):43853
    [Google Scholar]
  117. 117.
    Staropoli PC, Lee RK, Kroger ZA, Somohano K, Feldman M, et al. 2021.. Analysis of socioeconomic factors affecting follow-up in a glaucoma screening program. . Clin. Ophthalmol. 15::485563
    [Crossref] [Google Scholar]
  118. 118.
    Steinberg J, Iles MM, Lee JY, Wang X, Law MH, et al. 2022.. Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts. . Br. J. Dermatol. 186:(5):82334
    [Crossref] [Google Scholar]
  119. 119.
    Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, et al. 1997.. Identification of a gene that causes primary open angle glaucoma. . Science 275:(5300):66870
    [Crossref] [Google Scholar]
  120. 120.
    Tanigawa Y, Qian J, Venkataraman G, Justesen JM, Li R, et al. 2022.. Significant sparse polygenic risk scores across 813 traits in UK Biobank. . PLOS Genet. 18:(3):e1010105
    [Crossref] [Google Scholar]
  121. 121.
    Taylor HR, Pezzullo ML, Keeffe JE. 2006.. The economic impact and cost of visual impairment in Australia. . Br. J. Ophthalmol. 90:(3):27275
    [Crossref] [Google Scholar]
  122. 122.
    Tham Y-C, Li X, Wong TY, Quigley HA, Aung T, Cheng C-Y. 2014.. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. . Ophthalmology 121:(11):208190
    [Crossref] [Google Scholar]
  123. 123.
    Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. 1994.. Family history and risk of primary open angle glaucoma: the Baltimore Eye Survey. . Arch. Ophthalmol. 112:(1):6973
    [Crossref] [Google Scholar]
  124. 124.
    Tiller J, Bakshi A, Dowling G, Keogh L, McInerney-Leo A, et al. 2024.. Community concerns about genetic discrimination in life insurance persist in Australia: a survey of consumers offered genetic testing. . Eur. J. Hum. Genet. 32::28694. . 2024.. Eur. J. Hum. Genet. 32::365
    [Google Scholar]
  125. 125.
    Topouzis F, Coleman AL, Harris A, Koskosas A, Founti P, et al. 2008.. Factors associated with undiagnosed open-angle glaucoma: the Thessaloniki Eye Study. . Am. J. Ophthalmol. 145:(2):32735
    [Crossref] [Google Scholar]
  126. 126.
    Torkamani A, Wineinger NE, Topol EJ. 2018.. The personal and clinical utility of polygenic risk scores. . Nat. Rev. Genet. 19:(9):58190
    [Crossref] [Google Scholar]
  127. 127.
    Toth CA. 2023.. Optical coherence tomography and eye care. . N. Engl. J. Med. 389:(16):152629
    [Crossref] [Google Scholar]
  128. 128.
    Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, et al. 2018.. Multi-trait analysis of genome-wide association summary statistics using MTAG. . Nat. Genet. 50:(2):22937
    [Crossref] [Google Scholar]
  129. 129.
    UK Dep. Health Soc. Care. 2022.. Code on genetic testing and insurance. Guid. Doc. , UK Dep. Health Soc. Care, London:. https://www.gov.uk/government/publications/code-on-genetic-testing-and-insurance
    [Google Scholar]
  130. 130.
    van Koolwijk LME, Ramdas WD, Ikram MK, Jansonius NM, Pasutto F, et al. 2012.. Common genetic determinants of intraocular pressure and primary open-angle glaucoma. . PLOS Genet. 8:(5):e1002611
    [Crossref] [Google Scholar]
  131. 131.
    Vijaya L, George R, Baskaran M, Arvind H, Raju P, et al. 2008.. Prevalence of primary open-angle glaucoma in an urban south Indian population and comparison with a rural population: the Chennai Glaucoma Study. . Ophthalmology 115:(4):64854.e1
    [Crossref] [Google Scholar]
  132. 132.
    Waksmunski AR, Kinzy TG, Cruz LA, Nealon CL, Halladay CW, et al. 2022.. Glaucoma genetic risk scores in the Million Veteran Program. . Ophthalmology 129:(11):126374
    [Crossref] [Google Scholar]
  133. 133.
    Wallingford CK, Kovilpillai H, Jacobs C, Turbitt E, Primiero CA, et al. 2023.. Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: a systematic review. . Genet. Med. 25:(1):111
    [Crossref] [Google Scholar]
  134. 134.
    Wang K, Gaitsch H, Poon H, Cox NJ, Rzhetsky A. 2017.. Classification of common human diseases derived from shared genetic and environmental determinants. . Nat. Genet. 49:(9):131925
    [Crossref] [Google Scholar]
  135. 135.
    Wang Z, Wiggs JL, Aung T, Khawaja AP, Khor CC. 2022.. The genetic basis for adult onset glaucoma: recent advances and future directions. . Prog. Retin. Eye Res. 90::101066
    [Crossref] [Google Scholar]
  136. 136.
    Wedekind LE, Mahajan A, Hsueh W-C, Chen P, Olaiya MT, et al. 2023.. The utility of a type 2 diabetes polygenic score in addition to clinical variables for prediction of type 2 diabetes incidence in birth, youth and adult cohorts in an Indigenous study population. . Diabetologia 66:(5):84760
    [Crossref] [Google Scholar]
  137. 137.
    Weinreb RN, Khaw PT. 2004.. Primary open-angle glaucoma. . Lancet 363:(9422):171120
    [Crossref] [Google Scholar]
  138. 138.
    Wiggs JL, Pasquale LR. 2017.. Genetics of glaucoma. . Hum. Mol. Genet. 26:(R1):R2127
    [Crossref] [Google Scholar]
  139. 139.
    Wiggs JL, Yaspan BL, Hauser MA, Kang JH, Allingham RR, et al. 2012.. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. . PLOS Genet. 8:(4):e1002654
    [Crossref] [Google Scholar]
  140. 140.
    Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT. 1998.. Genetic risk of primary open-angle glaucoma: population-based familial aggregation study. . Arch. Ophthalmol. 116:(12):164045
    [Crossref] [Google Scholar]
  141. 141.
    Wong CK, Dite GS, Spaeth E, Murphy NM, Allman R. 2023.. Melanoma risk prediction based on a polygenic risk score and clinical risk factors. . Melanoma Res. 33:(4):29399
    [Crossref] [Google Scholar]
  142. 142.
    Yam GH-F, Gaplovska-Kysela K, Zuber C, Roth J. 2007.. Aggregated myocilin induces Russell bodies and causes apoptosis: implications for the pathogenesis of myocilin-caused primary open-angle glaucoma. . Am. J. Pathol. 170:(1):1009
    [Crossref] [Google Scholar]
  143. 143.
    Yanagi M, Kawasaki R, Wang JJ, Wong TY, Crowston J, Kiuchi Y. 2011.. Vascular risk factors in glaucoma: a review. . Clin. Exp. Ophthalmol. 39:(3):25258
    [Crossref] [Google Scholar]
  144. 144.
    Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, et al. 2010.. Common SNPs explain a large proportion of the heritability for human height. . Nat. Genet. 42:(7):56569
    [Crossref] [Google Scholar]
  145. 145.
    Young M-A, Yanes T, Cust AE, Dunlop K, Limb S, et al. 2023.. Human Genetics Society of Australasia position statement: use of polygenic scores in clinical practice and population health. . Twin Res. Hum. Genet. 26:(1):4048
    [Crossref] [Google Scholar]
  146. 146.
    Zebardast N, Sekimitsu S, Wang J, Elze T, Gharahkhani P, et al. 2021.. Characteristics of p.Gln368Ter myocilin variant and influence of polygenic risk on glaucoma penetrance in the UK Biobank. . Ophthalmology 128:(9):130011
    [Crossref] [Google Scholar]
  147. 147.
    Zheng Z, Liu S, Sidorenko J, Yengo L, Turley P, et al. 2022.. Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries. . bioRxiv 2022.10.12.510418. https://doi.org/10.1101/2022.10.12.510418
/content/journals/10.1146/annurev-genom-121222-105817
Loading
/content/journals/10.1146/annurev-genom-121222-105817
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error