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Fan, Q.* ; Verhoeven, V.J.* ; Wojciechowski, R.* ; Barathi, V.A.* ; Hysi, P.G.* ; Guggenheim, J.A.* ; Höhn, R.* ; Vitart, V.* ; Khawaja, A.P.* ; Yamashiro, K.* ; Hosseini, S.M.* ; Lehtimäki, T.* ; Lu, Y.* ; Haller, T.* ; Xie, J.* ; Delcourt, C.* ; Pirastu, M.* ; Wedenoja, J.* ; Gharahkhani, P.* ; Venturini, C.* ; Miyake, M.* ; Hewitt, A.W.* ; Guo, X.* ; Mazur, J.* ; Huffman, J.E.* ; Williams, K.M.* ; Polasek, O.* ; Campbell, H.* ; Rudan, I.* ; Vatavuk, Z.* ; Wilson, J.F.* ; Joshi, P.K.* ; McMahon, G.* ; St Pourcain, B.* ; Evans, D.M* ; Simpson, C.L.* ; Schwantes-An, T.H.* ; Igo, R.P.* ; Mirshahi, A.* ; Cougnard-Grégoire, A.* ; Bellenguez, C.* ; Blettner, M.* ; Raitakari, O.* ; Kähönen, M.* ; Seppälä, I.* ; Zeller, T.* ; Meitinger, T. ; Consortium for Refractive Error and Myopia (CREAM) (Döring, A.) ; Ried, J.S. ; Gieger, C. ; Portas, L.* ; van Leeuwen, E.M.* ; Amin, N.* ; Uitterlinden, A.G.* ; Rivadeneira, F.* ; Hofman, A.* ; Vingerling, J.R.* ; Wang, Y.X.* ; Wang, X.* ; Tai-Hui Boh, E.* ; Ikram, M.K.* ; Sabanayagam, C.* ; Gupta, P.* ; Tan, V.* ; Zhou, L.* ; Ho, C.E.* ; Lim, W.Y.* ; Beuerman, R.W.* ; Siantar, R.G.* ; Tai, E.S.* ; Vithana, E.* ; Mihailov, E.* ; Khor, C.C.* ; Hayward, C.* ; Luben, R.N.* ; Foster, P.J.* ; Klein, B.E.* ; Klein, R.* ; Wong, H.S.* ; Mitchell, P.* ; Metspalu, A.* ; Aung, T.* ; Young, T.L.* ; He, M.* ; Pärssinen, O.* ; van Duijn, C.M.* ; Wang, J.J.* ; Williams, C.* ; Jonas, J.B.* ; Teo, Y.Y.* ; Mackey, D.A.* ; Oexle, K.* ; Yoshimura, N.* ; Paterson, A.D.* ; Pfeiffer, N.* ; Wong, T.Y.* ; Baird, P.N.* ; Stambolian, D.* ; Wilson, J.E.* ; Cheng, C.Y.* ; Hammond, C.J.* ; Klaver, C.C.* ; Saw, S.M.*

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

Nat. Commun. 7:11008 (2016)

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Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

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