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

Publications // Young Lab // Aug 16 2019

PubMed ID: 31415580

Author(s): Wong YL, Hysi P, Cheung G, Tedja M, Hoang QV, Tompson SWJ, Whisenhunt KN, Verhoeven V, Zhao W, Hess M, Wong CW, Kifley A, Hosoda Y, Haarman AEG, Hopf S, Laspas P, Sensaki S, Sim X, Miyake M, Tsujikawa A, Lamoureux E, Ohno-Matsui K, Nickels S, Mitchell P, Wong TY, Wang JJ, Hammond CJ, Barathi VA, Cheng CY, Yamashiro K, Young TL, Klaver CCW, Saw SM; Consortium of Refractive Error, Myopia (CREAM). Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium. PLoS One. 2019 Aug 15;14(8):e0220143. doi: 10.1371/journal.pone.0220143. eCollection 2019. Erratum in: PLoS One. 2019 Oct 10;14(10):e0223942.

Journal: Plo S One, Volume 14, Issue 8, 2019

PURPOSE To 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).

METHODS A 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).

RESULTS In 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.

CONCLUSIONS Of 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.