Skip to main content
SpringerLink
Log in

The Genetics of Common, Complex Diseases

  • Reference work entry
  • First Online:
Albert and Jakobiec's Principles and Practice of Ophthalmology

  • 297 Accesses

Abstract

Common, age-related eye disorders are among the leading causes of vision impairment worldwide; these include but are not limited to age-related macular degeneration, glaucoma, Fuchs’ endothelial corneal dystrophy (FECD), and diabetic retinopathy. Each of these complex diseases offers an interesting example of the role of genetic (heritable) and nongenetic (environmental, lifestyle, etc.) risk factors. Herein we primarily review the genetic data relevant to these diseases, which have seen significant advances in the past 15 years, and highlight the next steps needed in order to bring clinical utility and ocular precision medicine to fruition.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 5,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 6,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. World report on vision [Internet]. [cited 2019 Dec 30]. Available from: https://www.who.int/publications-detail/world-report-on-vision

  2. Eye Disease Statistics – American Academy of Ophthalmology [Internet]. [cited 2020 Jan 16]. Available from: https://www.aao.org/eye-disease-statistics

  3. McPherson JD, Marra M, Hillier LD, Waterston RH, Chinwalla A, Wallis J, et al. A physical map of the human genome. Nature. 2001;409(6822):934–41.

    Article  CAS  PubMed  Google Scholar 

  4. Help Me Understand Genetics – Genetics Home Reference – NIH [Internet]. [cited 2020 Jan 16]. Available from: https://ghr.nlm.nih.gov/primer

  5. NLM NL of M. National Library of Medicine – National Institutes of Health.

    Google Scholar 

  6. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature [Internet]. 2009;461(7265):747–53. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/nature08494

    Article  CAS  PubMed Central  Google Scholar 

  7. Bush WS, Haines J. Overview of linkage analysis in complex traits. Curr Protoc Hum Genet [Internet]. 2010;64(1):1.9.1–1.9.18. [cited 2020 Jan 8]. Available from: http://doi.wiley.com/10.1002/0471142905.hg0109s64

    Google Scholar 

  8. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science (80-). 2005;308(5720):419–21.

    Article  CAS  Google Scholar 

  9. Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science (80-). 2005;308(5720):421–4.

    Article  CAS  Google Scholar 

  10. Seidman JG, Seidman C. Identifying candidate genes. Curr Protoc Hum Genet [Internet]. 2012;73(1):6.0.1–3. [cited 2020 Jan 8]. Available from: http://doi.wiley.com/10.1002/0471142905.hg0600s73

    Google Scholar 

  11. John S, Shephard N, Liu G, Zeggini E, Cao M, Chen W, et al. Whole-genome scan, in a complex disease, using 11,245 single-nucleotide polymorphisms: comparison with microsatellites. Am J Hum Genet. 2004;75(1):54–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guo X, Rotter JI. Genome-wide association studies. JAMA. 2019;322:1705–6.

    Article  PubMed  Google Scholar 

  13. Belmont JW, Boudreau A, Leal SM, Hardenbol P, Pasternak S, Wheeler DA, et al. A haplotype map of the human genome. Nature. 2005;437(7063):1299–320.

    Article  CAS  Google Scholar 

  14. Li Y, Willer C, Sanna S, Abecasis G. Genotype imputation. Annu Rev Genomics Hum Genet [Internet]. 2009;10(1):387–406. [cited 2020 Jan 16]. Available from: http://www.annualreviews.org/doi/10.1146/annurev.genom.9.081307.164242

    Article  CAS  Google Scholar 

  15. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res [Internet]. 2019;47(D1):D1005–12. [cited 2019 Aug 13]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30445434

    Article  CAS  Google Scholar 

  16. Sherry ST. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schwarze K, Buchanan J, Taylor JC, Wordsworth S. Are whole-exome and whole-genome sequencing approaches cost-effective? In: A systematic review of the literature. Vol. 20, Genetics in medicine. Nature Publishing Group; 2018. p. 1122–30.

    Google Scholar 

  18. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661–78.

    Article  CAS  Google Scholar 

  19. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med [Internet]. 2015;12(3):e1001779. [cited 2019 Oct 4]. Available from: https://dx.plos.org/10.1371/journal.pmed.1001779

    Article  Google Scholar 

  20. Gaziano JM, Concato J, Brophy M, Fiore L, Pyarajan S, Breeling J, et al. Million Veteran Program: a mega-biobank to study genetic influences on health and disease. J Clin Epidemiol. 2016;70:214–23.

    Article  PubMed  Google Scholar 

  21. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv [Internet]. 2019:531210. [cited 2020 Jan 15]. Available from: https://www.biorxiv.org/content/10.1101/531210v3

  23. NIH NHLBI, National Heart, Lung and BI. NHLBI Trans-Omics for Precision Medicine WGS-About TOPMed [Internet]. [cited 2020 Jan 15]. Available from: https://www.nhlbiwgs.org/

  24. Tyler AL, Crawford DC, Pendergrass SA. The detection and characterization of pleiotropy: discovery, progress, and promise. Brief Bioinform [Internet]. 2016;17(1):13–22. [cited 2019 Oct 5]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26223525

    Article  CAS  Google Scholar 

  25. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res [Internet]. 2019;47(D1):D1005–12. [cited 2019 Oct 4]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30445434

    Article  CAS  Google Scholar 

  26. Chesmore K, Bartlett J, Williams SM. The ubiquity of pleiotropy in human disease. Hum Genet. 2018;137(1):39–44.

    Article  CAS  PubMed  Google Scholar 

  27. Bush WS, Oetjens MT, Crawford DC. Unravelling the human genome-phenome relationship using phenome-wide association studies. Nature Reviews Genetics. 2016;17:129–45. Nature Publishing Group.

    Google Scholar 

  28. Sirugo G, Williams SM, Tishkoff SA. The missing diversity in human genetic studies. Cell [Internet]. 2019;177(1):26–31. [cited 2019 Oct 5]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30901543

    Article  CAS  Google Scholar 

  29. Need AC, Goldstein DB. Next generation disparities in human genomics: concerns and remedies. Trends Genet. 2009;25(11):489–94.

    Article  CAS  PubMed  Google Scholar 

  30. Popejoy AB, Fullerton SM. Genomics is failing on diversity. Nature. 2016;538:161–4. Nature Publishing Group.

    Google Scholar 

  31. Ginsburg GS, Phillips KA. Precision medicine: from science to value. Health Aff. 2018;37(5):694–701.

    Article  Google Scholar 

  32. NIH NI of H. National Institutes of Health (NIH) — All of Us [Internet]. [cited 2020 Jan 15]. Available from: https://allofus.nih.gov/

  33. Karow J. All of us program plans to return disease variants, PGx results, primary genomic data. 2018.

    Google Scholar 

  34. Crawford DC, Cooke Bailey JN, Briggs FBS. Mind the gap: resources required to receive, process and interpret research-returned whole genome data. Hum Genet 2019.

    Google Scholar 

  35. Igo RP, Kinzy TG, Cooke Bailey JN. Genetic risk scores. Curr Protoc Hum Genet. 2019;104(1):e95.

    PubMed  PubMed Central  Google Scholar 

  36. Verma A, Bang L, Miller JE, Zhang Y, Lee MTM, Zhang Y, et al. Human-disease phenotype map derived from PheWAS across 38,682 individuals. Am J Hum Genet [Internet]. 2019;104(1):55–64. [cited 2020 Jan 8]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30598166

    Article  CAS  Google Scholar 

  37. Salinas YD, Wang Z, DeWan AT. Statistical analysis of multiple phenotypes in genetic epidemiologic studies: from cross-phenotype associations to pleiotropy. Am J Epidemiol [Internet]. 2018;187(4):855–63. [cited 2019 Oct 5]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29020254

    Article  Google Scholar 

  38. Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabasi A-L. The human disease network. Proc Natl Acad Sci [Internet]. 2007;104(21):8685–90. [cited 2019 Oct 5]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17502601

    Article  CAS  Google Scholar 

  39. Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Heal. 2014;2:2.

    Google Scholar 

  40. Alasil T, Munoz N, Keane PA, Tufail A, Coady PA, Novais E, et al. Characteristics and racial variations of polypoidal choroidal vasculopathy in tertiary centers in the United States and United Kingdom. Int J Retin Vitr [Internet]. 2017 3(1). [cited 2021 Mar 23]. Available from: https://pubmed.ncbi.nlm.nih.gov/28428893/

  41. Fan Q, Cheung CMG, Chen LJ, Yamashiro K, Ahn J, Laude A, et al. Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. J Hum Genet [Internet]. 2017;62(12):1049–55. [cited 2021 Mar 23]. Available from: https://pubmed.ncbi.nlm.nih.gov/28835638/

    Article  Google Scholar 

  42. Silvestri G, Johnston PB, Hughes AE. Is genetic predisposition an important risk factor in age-related macular degeneration? Eye (Lond) [Internet]. 1994;8(Pt 5):564–8. [cited 2020 Jan 9]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7835454

    Article  Google Scholar 

  43. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am J Ophthalmol [Internet]. 1997;23(2):199–206. [cited 2020 Jan 9]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9186125

    Article  Google Scholar 

  44. Hammond CJ, Webster AR, Snieder H, Bird AC, Gilbert CE, Spector TD. Genetic influence on early age-related maculopathy: a twin study. Ophthalmology. 2002;109(4):730–6.

    Article  PubMed  Google Scholar 

  45. Shahid H, Khan JC, Cipriani V, Sepp T, Matharu BK, Bunce C, et al. Age-related macular degeneration: the importance of family history as a risk factor. Br J Ophthalmol. 2012;96(3):427–31.

    Article  PubMed  Google Scholar 

  46. Milton RC, Clemons TE, Klien R, Seddon JM, Ferris FL. Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS): AREDS report no. 19. Ophthalmology. 2005;112(4):533–539.e1.

    Article  PubMed  Google Scholar 

  47. DeAngelis MM, Ji F, Kim IK, Adams S, Capone A, Ott J, et al. Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. Arch Ophthalmol (Chicago, Ill 1960) [Internet]. 2007;125(1):49–54. [cited 2020 Jan 9]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17210851

    Article  CAS  Google Scholar 

  48. Igo RP, Kinzy TG, Cooke Bailey JN. Genetic risk scores. Curr Protoc Hum Genet. 2019;104:1.

    Google Scholar 

  49. Seddon JM, Cote J, Page WF, Aggen SH, Neale MC. The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. Arch Ophthalmol. 2005;123(3):321–7.

    Article  PubMed  Google Scholar 

  50. Penfold PL, Killingsworth MC, Sarks SH. Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol. 1985;223(2):69–76.

    Article  CAS  PubMed  Google Scholar 

  51. Abecasis GR, Yashar BM, Zhao Y, Ghiasvand NM, Zareparsi S, Branham KEH, et al. Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease. Am J Hum Genet [Internet]. 2004;74(3):482–94. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14968411

    Article  CAS  Google Scholar 

  52. Iyengar SK, Song D, Klein BEK, Klein R, Schick JH, Humphrey J, et al. Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. Am J Hum Genet [Internet]. 2004;74(1):20–39. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14691731

    Article  CAS  Google Scholar 

  53. Klein ML, Schultz DW, Edwards A, Matise TC, Rust K, Berselli CB, et al. Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q. Arch Ophthalmol (Chicago, Ill 1960) [Internet]. 1998;116(8):1082–8. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9715689

    Article  CAS  Google Scholar 

  54. Majewski J, Schultz DW, Weleber RG, Schain MB, Edwards AO, Matise TC, et al. Age-related macular degeneration – a genome scan in extended families. Am J Hum Genet [Internet]. 2003;73(3):540–50. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12900797

    Article  CAS  Google Scholar 

  55. Seddon JM, Santangelo SL, Book K, Chong S, Cote J. A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions. Am J Hum Genet [Internet]. 2003;73(7):780–90. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12945014

    Article  CAS  Google Scholar 

  56. Weeks DE, Conley YP, Mah TS, Paul TO, Morse L, Ngo-Chang J, et al. A full genome scan for age-related maculopathy. Hum Mol Genet [Internet]. 2000;9(9):1329–49. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10814715

    Article  CAS  Google Scholar 

  57. Weeks DE, Conley YP, Tsai HJ, Mah TS, Rosenfeld PJ, Paul TO, et al. Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions. Am J Ophthalmol. 2001;132(5):682–92.

    Article  CAS  PubMed  Google Scholar 

  58. Weeks DE, Conley YP, Tsai H-J, Mah TS, Schmidt S, Postel EA, et al. Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. Am J Hum Genet [Internet]. 2004;75(2):174–89. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15168325

    Article  CAS  Google Scholar 

  59. Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK, et al. Meta-analysis of genome scans of age-related macular degeneration. Hum Mol Genet [Internet]. 2005;14(15):2257–64. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15987700

    Article  CAS  Google Scholar 

  60. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science (80-). 2005;308(5720):385–9.

    Article  CAS  Google Scholar 

  61. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005;102(20):7227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wagner EK, Raychaudhuri S, Villalonga MB, Java A, Triebwasser MP, Daly MJ, et al. Mapping rare, deleterious mutations in Factor H: association with early onset, drusen burden, and lower antigenic levels in familial AMD. Sci Rep [Internet]. 2016;6. [cited 2021 Mar 23]. Available from: https://pubmed.ncbi.nlm.nih.gov/27572114/

  63. Raychaudhuri S, Iartchouk O, Chin K, Tan PL, Tai AK, Ripke S, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. Nat Genet [Internet]. 2011;43(12):1232–6. [cited 2021 Mar 23]. Available from: https://pubmed.ncbi.nlm.nih.gov/22019782/

    Article  CAS  Google Scholar 

  64. Duvvari MR, Saksens NTM, van de Ven JPH, de Jong-Hesse Y, Schick T, Nillesen WM, et al. Analysis of rare variants in the CFH gene in patients with the cuticular drusen subtype of age-related macular degeneration. Mol Vis [Internet]. 2015;21:285–92. [cited 2021 Mar 23]. Available from: http://www.molvis.org/molvis/v21/285

    CAS  Google Scholar 

  65. Schellevis RL, Van Dijk EHC, Breukink MB, Altay L, Bakker B, Koeleman BPC, et al. Role of the complement system in chronic central serous chorioretinopathy: a genome-wide association study. JAMA Ophthalmol. 2018;136(10):1128–36.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yuan D, Yang Q, Liu X, Yuan D, Yuan S, Xie P, et al. Complement factor H Val62Ile variant and risk of age-related macular degeneration: a meta-analysis. Mol Vis. 2013;19:374–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Fan Q, Cheung CMG, Chen LJ, Yamashiro K, Ahn J, Laude A, et al. Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. J Hum Genet. 2017;62(12):1049–55.

    Article  PubMed  Google Scholar 

  68. Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB. Susceptibility genes for age-related maculopathy on chromosome 10q26. Am J Hum Genet. 2005;77(3):389–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet [Internet]. 2005;14(21):3227–36. [cited 2020 Jan 10]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16174643

    Article  CAS  Google Scholar 

  70. DeWan A, Liu M, Hartman S, Zhang SSM, Liu DTL, Zhao C, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science (80-). 2006;314(5801):989–92.

    Article  CAS  Google Scholar 

  71. Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science (80-). 2006;314(5801):992–3.

    Article  CAS  Google Scholar 

  72. Grassmann F, Heid IM, Weber BHF, Fritsche LG, Igl W, Bailey JN, et al. Recombinant haplotypes narrow the ARMS2/HTRA1 association signal for age-related macular degeneration. Genetics. 2017;205(2):919–24.

    Article  CAS  PubMed  Google Scholar 

  73. DeAngelis MM, Owen LA, Morrison MA, Morgan DJ, Li M, Shakoor A, et al. Genetics of age-related macular degeneration (AMD). Hum Mol Genet [Internet]. 2017;26(R2):R246. [cited 2020 Jan 9]. Available from: https://academic.oup.com/hmg/article/26/R2/R246/4283038

    Article  CAS  Google Scholar 

  74. Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y, Thorleifsson G, et al. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013;45(4):433–9.

    Article  CAS  PubMed  Google Scholar 

  75. Fritsche LG, Igl W, Bailey JNC, Grassmann F, Sengupta S, Bragg-Gresham JL, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet [Internet]. 2016;48(2):134–43. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/ng.3448

    Article  CAS  Google Scholar 

  76. Cooke Bailey J, Hoffman J, Sardell R, Scott W, Pericak-Vance M, Haines J. The application of genetic risk scores in age-related macular degeneration: a review. J Clin Med. 2016;5(3):31.

    Article  PubMed Central  CAS  Google Scholar 

  77. Igo RP, Cooke Bailey JN. Genetic risk scores in complex eye disorders. In: Genetics and genomics of eye disease. Elsevier; 2020. p. 259–75.

    Chapter  Google Scholar 

  78. Awh CC, Hawken S, Zanke BW. Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the age-related eye disease study. Ophthalmology. 2015;122(1):162–9.

    Article  PubMed  Google Scholar 

  79. Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013;120(11):2317–23.

    Article  PubMed  Google Scholar 

  80. Chew EY, Klein ML, Clemons TE, Agrón E, Ratnapriya R, Edwards AO, et al. No clinically significant association between CFH and ARMS2 genotypes and response to nutritional supplements: AREDS report number 38. Ophthalmology. 2014;121(11):2173–80.

    Article  PubMed  Google Scholar 

  81. Hagstrom SA, Ying GS, Pauer GJT, Sturgill-Short GM, Huang J, Callanan DG, et al. Pharmacogenetics for genes associated with age-related macular degeneration in the comparison of AMD treatments trials (CATT). Ophthalmology. 2013;120(3):593–9.

    Article  PubMed  Google Scholar 

  82. Chew EY, Klein ML, Clemons TE, Agrón E, Abecasis GR. Genetic testing in persons with age-related macular degeneration and the use of the AREDS supplements: to test or not to test? Ophthalmology. 2015;122(1):212–5.

    Article  PubMed  Google Scholar 

  83. Lotery AJ, Gibson J, Cree AJ, Downes SM, Harding SP, Rogers CA, et al. Pharmacogenetic associations with vascular endothelial growth factor inhibition in participants with neovascular age-related macular degeneration in the Ivan study. Ophthalmology. 2013;120(12):2637–43.

    Article  PubMed  Google Scholar 

  84. Restrepo NA, Spencer KL, Goodloe R, Garrett TA, Heiss G, Bůžková P, et al. Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study. Invest Ophthalmol Vis Sci. 2014;55(10):6839–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Restrepo NA, Mitchell SL, Goodloe RJ, Murdock DG, Haines JL, Crawford DC. Mitochondrial variation and the risk of age-related macular degeneration across diverse populations. In: Pacific symposium on biocomputing; 2015. p. 243–54.

    Google Scholar 

  86. Sanfilippo PG, Hewitt AW, Hammond CJ, Mackey DA. The heritability of ocular traits. Surv Ophthalmol [Internet]. 2010;55(6):561–83. [cited 2019 Jun 24]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S003962571000144X

    Article  Google Scholar 

  87. Asefa NG, Neustaeter A, Jansonius NM, Snieder H. Heritability of glaucoma and glaucoma-related endophenotypes: systematic review and meta-analysis. Surv Ophthalmol. 2019;64(6):835–51.

    Article  PubMed  Google Scholar 

  88. Springelkamp H, Höhn R, Mishra A, Hysi PG, Khor C-C, Loomis SJ, et al. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun. 2014;5.

    Google Scholar 

  89. Wang K, Gaitsch H, Poon H, Cox NJ, Rzhetsky A. Classification of common human diseases derived from shared genetic and environmental determinants. Nat Genet. 2017;49(9):1319–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Choquet H, Paylakhi S, Kneeland SC, Thai KK, Hoffmann TJ, Yin J, et al. A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci. Nat Commun [Internet]. 2018;9(1):2278. [cited 2020 Jan 7]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29891935

    Article  CAS  Google Scholar 

  91. Ge T, Chen CY, Neale BM, Sabuncu MR, Smoller JW. Phenome-wide heritability analysis of the UK Biobank. PLoS Genet. 2017;1:13(4).

    Google Scholar 

  92. Polubriaginof FCG, Vanguri R, Quinnies K, Belbin GM, Yahi A, Salmasian H, et al. Disease heritability inferred from familial relationships reported in medical records. Cell. 2018;173(7):1692–1704.e11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Wiggs JL. Glaucoma genes and mechanisms. Prog Mol Biol Transl Sci [Internet]. 2015;134:315–42. [cited 2019 Oct 30]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26310163

    Article  Google Scholar 

  94. Doucette LP, Rasnitsyn A, Seifi M, Walter MA. The interactions of genes, age, and environment in glaucoma pathogenesis. Surv Ophthalmol. 2015.

    Google Scholar 

  95. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014.

    Google Scholar 

  96. National Eye Institute. Glaucoma, Open-angle | National Eye Institute [Internet]. [cited 2019 Jan 31]. Available from: https://nei.nih.gov/eyedata/glaucoma

  97. Caprioli J. Glaucoma: a disease of early cellular senescence. Investig Ophthalmol Vis Sci. 2013.

    Google Scholar 

  98. Wiggs JL, Pasquale LR. Genetics of glaucoma. 26, Human molecular genetics. Oxford University Press; 2017. p. R21–R27.

    Google Scholar 

  99. Kwon YH, Fingert JH, Kuehn MH, Alward WLM. Mechanism of disease: primary open-angle glaucoma. N Engl J Med. 2009;360(11):1113–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Alward WLM, van der Heide C, Khanna CL, Roos BR, Sivaprasad S, Kam J, et al. Myocilin mutations in patients with normal-tension glaucoma. JAMA Ophthalmol [Internet]. 2019;137(5):559. [cited 2019 Jun 30]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30816940

    Article  Google Scholar 

  101. Sears NC, Boese EA, Miller MA, Fingert JH. Mendelian genes in primary open angle glaucoma, vol. 186. Experimental Eye Research: Academic; 2019.

    Google Scholar 

  102. Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol (Chicago, Ill 1960) [Internet]. 2007;125(1):30–7. [cited 2019 Jun 24]. Available from: http://archopht.jamanetwork.com/article.aspx?doi=10.1001/archopht.125.1.30

    Article  CAS  Google Scholar 

  103. Zebardast N, Sekimitsu S, Wang J, Elze T, Gharahkhani P, Cole BS, et al. Characteristics of Gln368Ter Myocilin variant and influence of polygenic risk on glaucoma penetrance in the UK Biobank. Ophthalmology [Internet]. 2021. [cited 2021 Mar 18]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0161642021001895

  104. Souma T, Tompson SW, Thomson BR, Siggs OM, Kizhatil K, Yamaguchi S, et al. Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity. J Clin Invest [Internet]. 2016;126(7):2575–87. [cited 2019 Jun 24]. Available from: https://www.jci.org/articles/view/85830

    Article  Google Scholar 

  105. Iglesias AI, Mishra A, Vitart V, Bykhovskaya Y, Höhn R, Springelkamp H, et al. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nat Commun. 2018;9:1.

    Article  CAS  Google Scholar 

  106. Ritch R, Steinberger D, Liebmann JM. Prevalence of pigment dispersion syndrome in a population undergoing glaucoma screening. Am J Ophthalmol [Internet]. 1993;115(6):707–10. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8506904

    Article  CAS  Google Scholar 

  107. Hiller R, Sperduto RD, Krueger DE. Pseudoexfoliation, intraocular pressure, and senile lens changes in a population-based survey. Arch Ophthalmol (Chicago, Ill 1960) [Internet]. 1982;100(7):1080–2. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7092647

    Article  CAS  Google Scholar 

  108. Quigley H, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bailey JNC, Loomis SJ, Kang JH, Allingham RR, Gharahkhani P, Khor CC, et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet. 2016;48:2.

    Article  CAS  Google Scholar 

  110. Shiga Y, Akiyama M, Nishiguchi KM, Sato K, Shimozawa N, Takahashi A, et al. Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. Hum Mol Genet. 2018;27:8.

    Article  CAS  Google Scholar 

  111. MacGregor S, Ong J-S, An J, Han X, Zhou T, Siggs OM, et al. Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. Nat Genet [Internet]. 2018;50(8):1067–71. [cited 2019 Jun 30]. Available from: http://www.nature.com/articles/s41588-018-0176-y

    Article  CAS  Google Scholar 

  112. Burdon KP, MacGregor S, Hewitt AW, Sharma S, Chidlow G, Mills RA, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet [Internet]. 2011;43(6):574–8. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21532571

    Article  CAS  Google Scholar 

  113. Chen Y, Lin Y, Vithana EN, Jia L, Zuo X, Wong TY, et al. Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma. Nat Genet [Internet]. 2014;46(10):1115–9. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/ng.3078

    Article  CAS  Google Scholar 

  114. Gharahkhani P, Burdon KP, Fogarty R, Sharma S, Hewitt AW, Martin S, et al. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nat Genet [Internet]. 2014;46(10):1120–5. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/ng.3079

    Article  CAS  Google Scholar 

  115. Hysi PG, Cheng C-Y, Springelkamp H, Macgregor S, Cooke Bailey JN, Wojciechowski R, et al. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nat Genet. 2014;46:10.

    Article  CAS  Google Scholar 

  116. Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015;24:13.

    Article  CAS  Google Scholar 

  117. Thorleifsson G, Walters GB, Hewitt AW, Masson G, Helgason A, DeWan A, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet [Internet]. 2010;42(10):906–9. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20835238

    Article  CAS  Google Scholar 

  118. Wiggs JL, Yaspan BL, Hauser MA, Kang JH, Allingham RR, Olson LM, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. Barsh GS, editor. PLoS Genet [Internet]. 2012 8(4):e1002654. [cited 2019 Jun 24]. Available from: http://dx.plos.org/10.1371/journal.pgen.1002654

  119. Gharahkhani P, Burdon KP, Cooke Bailey JN, Hewitt AW, Law MH, Pasquale LR, et al. Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma. Sci Rep [Internet]. 2018;8(1):3124. [cited 2020 Jan 7]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29449654

    Article  CAS  Google Scholar 

  120. Aung T, Ozaki M, Lee MC, Schlötzer-Schrehardt U, Thorleifsson G, Mizoguchi T, et al. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat Genet [Internet]. 2017;49(7):993–1004. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/ng.3875

    Article  CAS  Google Scholar 

  121. Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet [Internet]. 2016;48(5):556–62. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27064256

    Article  CAS  Google Scholar 

  122. Paschoud S, Jond L, Guerrera D, Citi S. PLEKHA7 modulates epithelial tight junction barrier function. Tissue Barriers [Internet]. 2014;2(2):e28755. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24843844

    Article  Google Scholar 

  123. Vithana EN, Khor C-C, Qiao C, Nongpiur ME, George R, Chen L-J, et al. Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. Nat Genet [Internet]. 2012;44(10):1142–6. [cited 2019 Jun 24]. Available from: http://www.nature.com/articles/ng.2390

    Article  CAS  PubMed Central  Google Scholar 

  124. Wiggs JL. Glaucoma genes and mechanisms. In: Progress in molecular biology and translational science [Internet]; 2015. p. 315–42. [cited 2019 Jun 24]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1877117315000691.

    Google Scholar 

  125. Springelkamp H, Iglesias AI, Mishra A, Höhn R, Wojciechowski R, Khawaja AP, et al. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. Hum Mol Genet. 2017;26:2.

    CAS  Google Scholar 

  126. Choquet H, Wiggs JL, Khawaja AP. Clinical implications of recent advances in primary open-angle glaucoma genetics. Eye (Basingstoke): Nature Publishing Group; 2019.

    Google Scholar 

  127. Lahola-Chomiak AA, Walter MA. Molecular genetics of pigment dispersion syndrome and pigmentary glaucoma: new insights into mechanisms. J Ophthalmol [Internet]. 2018;2018:5926906. [cited 2019 Jun 24]. Available from: https://www.hindawi.com/journals/joph/2018/5926906/

    Google Scholar 

  128. Lahola-Chomiak AA, Footz T, Nguyen-Phuoc K, Neil GJ, Fan B, Allen KF, et al. Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma. Hum Mol Genet [Internet]. 2019;28(8):1298–311. [cited 2019 Jun 30]. Available from: https://academic.oup.com/hmg/article/28/8/1298/5248265

    Article  CAS  Google Scholar 

  129. Aung T, Chan AS, Khor C-C. Genetics of exfoliation syndrome. J Glaucoma [Internet]. 2018;27:S12–4. [cited 2020 Jan 13]. Available from: http://insights.ovid.com/crossref?an=00061198-201807001-00003

    Article  Google Scholar 

  130. Thorleifsson G, Magnusson KP, Sulem P, Walters GB, Gudbjartsson DF, Stefansson H, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science (80-) [Internet]. 2007;317(5843):1397–400. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17690259

    Article  CAS  Google Scholar 

  131. Wiggs JL, Pasquale LR. Genetics of glaucoma. In: Human molecular genetics; 2017.

    Google Scholar 

  132. Williams SEI, Whigham BT, Liu Y, Carmichael TR, Qin X, Schmidt S, et al. Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population. Mol Vis. 2010;16:705–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Aung T, Ozaki M, Mizoguchi T, Allingham RR, Li Z, Haripriya A, et al. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nat Genet. 2015;47:4.

    Google Scholar 

  134. Richards AJ, McNinch A, Martin H, Oakhill K, Rai H, Waller S, et al. Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Hum Mutat [Internet]. 2010;31(6):E1461–71. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20513134

    Article  CAS  Google Scholar 

  135. Wang J, Yusufu M, Khor CC, Aung T, Wang N. The genetics of angle closure glaucoma. In: Experimental eye research, vol. 189. Academic; 2019.

    Google Scholar 

  136. Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, et al. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat Commun [Internet]. 2021;12(1):1258. [cited 2021 Mar 17]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33627673

    Article  CAS  Google Scholar 

  137. Bonnemaijer PWM, Leeuwen EM, Iglesias AI, Gharahkhani P, Vitart V, Khawaja AP, et al. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Commun Biol. 2019;2:1.

    Article  Google Scholar 

  138. Springelkamp H, Mishra A, Hysi PG, Gharahkhani P, Höhn R, Khor C-C, et al. Meta-analysis of genome-wide association studies identifies novel loci associated with optic disc morphology. Genet Epidemiol [Internet]. 2015;39(3):207–16. [cited 2019 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25631615

    Article  Google Scholar 

  139. Tham YC, Liao J, Vithana EN, Khor CC, Teo YY, Tai ES, et al. Aggregate effects of intraocular pressure and cup-to-disc ratio genetic variants on glaucoma in a multiethnic Asian population. Ophthalmology. 2015;122(6):1149–57.

    Article  PubMed  Google Scholar 

  140. Nag A, Venturini C, Small KS, International Glaucoma Genetics Consortium, Young TL, Viswanathan AC, et al. A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort. Hum Mol Genet [Internet]. 2014;23(12):3343–8. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24518671

    Article  CAS  Google Scholar 

  141. Iglesias AI, Ong JS, Khawaja AP, Gharahkhani P, Tedja MS, Verhoeven VJM, et al. Determining possible shared genetic architecture between myopia and primary open-angle glaucoma. Invest Ophthalmol Vis Sci [Internet]. 2019;60(8):3142–9. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31323684

    Article  CAS  Google Scholar 

  142. King R, Struebing FL, Li Y, Wang J, Koch AA, Cooke Bailey JN, et al. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma. PLoS Genet [Internet]. 2018;14(1):e1007145. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29370175

    Article  CAS  Google Scholar 

  143. Aschard H, Kang JH, Iglesias AI, Hysi P, Cooke Bailey JN, Khawaja AP, et al. Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis. Eur J Hum Genet [Internet]. 2017;25(11):1261–7. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28853718

    Article  Google Scholar 

  144. Fan BJ, Chen X, Sondhi N, Sharmila PF, Soumittra N, Sripriya S, et al. Family-based genome-wide association study of South Indian pedigrees supports WNT7B as a central corneal thickness locus. Invest Ophthalmol Vis Sci [Internet]. 2018;59(6):2495–502. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29847655

    Article  CAS  Google Scholar 

  145. Laville V, Kang JH, Cousins CC, Iglesias AI, Nagy R, Cooke Bailey JN, et al. Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes. Am J Ophthalmol [Internet]. 2019. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31121135

  146. Chintalapudi SR, Maria D, Di Wang X, Bailey JNC, Allingham R, Brilliant M, et al. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Nat Commun. 2017;8:1.

    Article  CAS  Google Scholar 

  147. Iglesias AI, van der Lee SJ, Bonnemaijer PWM, Höhn R, Nag A, Gharahkhani P, et al. Haplotype reference consortium panel: practical implications of imputations with large reference panels. Hum Mutat. 2017;38(8):1025–32.

    Article  CAS  PubMed  Google Scholar 

  148. Gao X, Nannini DR, Corrao K, Torres M, Chen Y-DI, Fan BJ, et al. Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos. Hum Mol Genet [Internet]. 2016;25(22):5035–45. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28171582

    CAS  Google Scholar 

  149. Khachatryan N, Medeiros FA, Sharpsten L, Bowd C, Sample PA, Liebmann JM, et al. The African descent and glaucoma evaluation study (ADAGES): predictors of visual field damage in glaucoma suspects. Am J Ophthalmol. 2015;

    Google Scholar 

  150. Kyari F, Abdull MM, Bastawrous A, Gilbert CE, Faal H. Epidemiology of glaucoma in Sub-Saharan Africa: prevalence, incidence and risk factors. Middle East Afr J Ophthalmol. 2013:111–25.

    Google Scholar 

  151. Julia Salinas RS, Aishat Mohammed NHF, Warren JZ. Primary open-angle glaucoma in individuals of African descent: a review of risk factors. J Clin Exp Ophthalmol 2015.

    Google Scholar 

  152. Pleet A, Sulewski M, Salowe RJ, Fertig R, Salinas J, Rhodes A, et al. Risk factors associated with progression to blindness from primary open-angle glaucoma in an African-American population. Ophthalmic Epidemiol. 2016.

    Google Scholar 

  153. Restrepo NA, Cooke Bailey JN. Primary open-angle glaucoma genetics in African Americans. Curr Genet Med Rep. 2017.

    Google Scholar 

  154. Taylor KD, Guo X, Zangwill LM, Liebmann JM, Girkin CA, Feldman RM, et al. Genetic architecture of primary open-angle glaucoma in individuals of African descent: the African descent and glaucoma evaluation study III. Ophthalmology [Internet]. 2019;126(1):38–48. [cited 2019 Jul 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30352225

    Article  Google Scholar 

  155. Bonnemaijer PWM, Iglesias AI, Nadkarni GN, Sanyiwa AJ, Hassan HG, Cook C, et al. Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations. Hum Genet [Internet]. 2018;137(10):847–62. [cited 2019 Jul 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30317457

    Article  CAS  Google Scholar 

  156. Genetics of Glaucoma in People of African Descent (GGLAD) Consortium, Hauser MA, Allingham RR, Aung T, Van Der Heide CJ, Taylor KD, et al. Association of genetic variants with primary open-angle glaucoma among individuals with African ancestry. JAMA [Internet]. 2019;322(17):1682–91. [cited 2020 Jan 6]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31688885

    Article  Google Scholar 

  157. Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, et al. A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease [Internet]. bioRxiv. 2020:2020.01.30.927822. [cited 2021 Feb 3]. Available from: https://doi.org/10.1101/2020.01.30.927822

  158. Fan BJ, Bailey JC, Igo RP, Kang JH, Boumenna T, Brilliant MH, et al. Association of a primary open-angle glaucoma genetic risk score with earlier age at diagnosis. JAMA Ophthalmol. 2019;137(10):1190–4.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Han X, Hewitt AW, MacGregor S. Predicting the future of genetic risk profiling of glaucoma: a narrative review. JAMA Ophthalmol [Internet]. 2020;139(2):224–31. [cited 2021 Mar 18]. Available from: https://jamanetwork.com/

    Article  Google Scholar 

  160. Wong EHF, Fox JC, Ng MYM, Lee CM. Toward personalized medicine in the neuropsychiatric field. Int Rev Neurobiol. 2011;101:329–49.

    Article  PubMed  Google Scholar 

  161. van Koolwijk LME, Ramdas WD, Ikram MK, Jansonius NM, Pasutto F, Hysi PG, et al. Common genetic determinants of intraocular pressure and primary open-angle Glaucoma. PLoS Genet. 2012;8:5.

    Google Scholar 

  162. Ramdas WD, van Koolwijk LME, Ikram MK, Jansonius NM, de Jong PTVM, Bergen AAB, et al. A genome-wide association study of optic disc parameters. PLoS Genet. 2010;6(6):1–12.

    Article  CAS  Google Scholar 

  163. Charlesworth J, Kramer PL, Dyer T, Diego V, Samples JR, Craig JE, et al. The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness. Investig Ophthalmol Vis Sci. 2010;51(7):3509–14.

    Article  Google Scholar 

  164. Khawaja AP, Cooke Bailey JN, Wareham NJ, Scott RA, Simcoe M, Igo RP, et al. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet. 2018;50:6.

    Article  CAS  Google Scholar 

  165. Choquet H, Thai KK, Yin J, Hoffmann TJ, Kvale MN, Banda Y, et al. A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure. Nat Commun [Internet]. 2017;8(1):2108. [cited 2020 Jan 7]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29235454

    Article  CAS  Google Scholar 

  166. Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh PR, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cuellar-Partida G, Craig JE, Burdon KP, Wang JJ, Vote BJ, Souzeau E, et al. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration. Sci Rep. 2016;31:6.

    Google Scholar 

  168. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.

    Article  CAS  PubMed  Google Scholar 

  169. Congdon N. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004.

    Google Scholar 

  170. Diabetic Retinopathy – silently blinding millions of people world-wide • IAPB Vision Atlas [Internet]. [cited 2020 Jan 11]. Available from: http://atlas.iapb.org/vision-trends/diabetic-retinopathy/

  171. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis. 2015;2:1.

    Article  Google Scholar 

  172. Hietala K, Forsblom C, Summanen P, Groop P-H, FinnDiane Study Group. Heritability of proliferative diabetic retinopathy. Diabetes [Internet]. 2008;57(8):2176–80. [cited 2020 Jan 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18443200

    Article  CAS  Google Scholar 

  173. Looker HC, Nelson RG, Chew E, Klein R, Klein BEK, Knowler WC, et al. Genome-wide linkage analyses to identify loci for diabetic retinopathy. Diabetes. 2007;56(4):1160–6.

    Article  CAS  PubMed  Google Scholar 

  174. Eghrari AO, Gottsch JD. Fuchs corneal dystrophy. Exp Rev Ophthalmol. 2010;5:147–59.

    Article  Google Scholar 

  175. Musch DC, Niziol LM, Stein JD, Kamyar RM, Sugar A. Prevalence of corneal dystrophies in the United States: estimates from claims data. Investig Ophthalmol Vis Sci. 2011;52(9):6959–63.

    Article  Google Scholar 

  176. Hamill CE, Schmedt T, Jurkunas U. Fuchs endothelial cornea dystrophy: a review of the genetics behind disease development. Semin Ophthalmol [Internet]. 28(5–6):281–6. [cited 2020 Jan 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24138036

  177. Louttit MD, Kopplin LJ, Igo RP, Fondran JR, Tagliaferri A, Bardenstein D, et al. A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability. Cornea. 2012;31(1):26–35.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Li Y-J, Minear MA, Rimmler J, Zhao B, Balajonda E, Hauser MA, et al. Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS One [Internet]. 2011;6(4):e18044. [cited 2020 Jan 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21533127

    Article  CAS  Google Scholar 

  179. Baratz KH, Tosakulwong N, Ryu E, Brown WL, Branham K, Chen W, et al. E2-2 protein and Fuchs’s corneal dystrophy. N Engl J Med. 2010;363(11):1016–24.

    Article  CAS  PubMed  Google Scholar 

  180. Wieben ED, Aleff RA, Tosakulwong N, Butz ML, Highsmith WE, Edwards AO, et al. A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS One [Internet]. 2012;7(11):e49083. [cited 2020 Jan 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23185296

    Article  CAS  Google Scholar 

  181. Igo RP, Kopplin LJ, Joseph P, Truitt B, Fondran J, Bardenstein D, et al. Differing roles for TCF4 and COL8A2 in central corneal thickness and fuchs endothelial corneal dystrophy. PLoS One [Internet]. 2012;7(10):e46742. [cited 2020 Jan 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23110055

    Article  CAS  Google Scholar 

  182. Kuot A, Hewitt AW, Griggs K, Klebe S, Mills R, Jhanji V, et al. Association of TCF4 and CLU polymorphisms with Fuchs endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. Eur J Hum Genet. 2012;20(6):632–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Afshari NA, Igo RP, Morris NJ, Stambolian D, Sharma S, Pulagam VL, et al. Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy. Nat Commun. 2017;30:8.

    Google Scholar 

  184. AAO AA of O. Recommendations on Clinical Assessment of Patients with Inherited Retinal Degenerations – 2016 – American Academy of Ophthalmology [Internet]. [cited 2020 Jan 15]. Available from: https://www.aao.org/clinical-statement/recommendations-on-clinical-assessment-of-patients

  185. Buitendijk GHS, Amin N, Hofman A, van Duijn CM, Vingerling JR, Klaver CCW. Direct-to-consumer personal genome testing for age-related macular degeneration. Investig Ophthalmol Vis Sci. 2014;55(10):6167–74.

    Article  CAS  Google Scholar 

  186. Kalf RRJ, Mihaescu R, Kundu S, de Knijff P, Green RC, Janssens ACJW. Variations in predicted risks in personal genome testing for common complex diseases. Genet Med [Internet]. 2014;16(1):85–91. [cited 2020 Jan 7]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23807614

    Article  Google Scholar 

  187. Seddon JM, George S, Rosner B, Klein ML. CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Hum Hered [Internet]. 2006;61(3):157–65. [cited 2021 Mar 23]. Available from: https://pubmed.ncbi.nlm.nih.gov/16816528/

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA

    Jessica N. Cooke Bailey

  2. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA

    Jessica N. Cooke Bailey

  3. Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA

    Lucia Sobrin & Janey L. Wiggs

Authors
  1. Jessica N. Cooke Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucia Sobrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janey L. Wiggs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jessica N. Cooke Bailey .

Editor information

Editors and Affiliations

  1. Casey Eye Institute, Oregon Health & Science, Portland, OR, USA

    Daniel M. Albert

  2. Department of Ophthalmology, Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Joan W. Miller

  3. Department of Ophthalmology, University of Illinois College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Dimitri T. Azar

  4. Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA

    Lucy H. Young

Section Editor information

  1. Massachusetts Eye and Ear, Boston, USA

    Jason Comander

  2. Massachusetts Eye and Ear, Boston, USA

    Luk Vandenberghe

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Cooke Bailey, J.N., Sobrin, L., Wiggs, J.L. (2022). The Genetics of Common, Complex Diseases. In: Albert, D.M., Miller, J.W., Azar, D.T., Young, L.H. (eds) Albert and Jakobiec's Principles and Practice of Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-030-42634-7_151

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-42634-7_151

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-42633-0

  • Online ISBN: 978-3-030-42634-7

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation