PLoS ONE (Jan 2019)

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

  • Yee-Ling Wong,
  • Pirro Hysi,
  • Gemmy Cheung,
  • Milly Tedja,
  • Quan V Hoang,
  • Stuart W J Tompson,
  • Kristina N Whisenhunt,
  • Virginie Verhoeven,
  • Wanting Zhao,
  • Moritz Hess,
  • Chee-Wai Wong,
  • Annette Kifley,
  • Yoshikatsu Hosoda,
  • Annechien E G Haarman,
  • Susanne Hopf,
  • Panagiotis Laspas,
  • Sonoko Sensaki,
  • Xueling Sim,
  • Masahiro Miyake,
  • Akitaka Tsujikawa,
  • Ecosse Lamoureux,
  • Kyoko Ohno-Matsui,
  • Stefan Nickels,
  • Paul Mitchell,
  • Tien-Yin Wong,
  • Jie Jin Wang,
  • Christopher J Hammond,
  • Veluchamy A Barathi,
  • Ching-Yu Cheng,
  • Kenji Yamashiro,
  • Terri L Young,
  • Caroline C W Klaver,
  • Seang-Mei Saw,
  • Consortium of Refractive Error, Myopia (CREAM)

DOI
https://doi.org/10.1371/journal.pone.0220143
Journal volume & issue
Vol. 14, no. 8
p. e0220143

Abstract

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PurposeTo evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM).MethodsA candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM).ResultsIn the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance.ConclusionsOf the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.