1. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
- Author
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Aung, T., Ozaki, M., Lee, M.C., Schlotzer-Schrehardt, U., Thorleifsson, G., Mizoguchi, T., Igo, R.P., Jr., Haripriya, A., Williams, S.E., Astakhov, Y.S., Orr, A.C., Burdon, K.P., Nakano, S., Mori, K., Abu-Amero, K., Hauser, M., Li, Z., Prakadeeswari, G., Bailey, J.N., Cherecheanu, A.P., Kang, J.H., Nelson, S., Hayashi, K., Manabe, S.I., Kazama, S., Zarnowski, T., Inoue, K., Irkec, M., Coca-Prados, M., Sugiyama, K., Jarvela, I., Schlottmann, P., Lerner, S.F., Lamari, H., Nilgun, Y., Bikbov, M., Park, K.H., Cha, S.C., Yamashiro, K., Zenteno, J.C., Jonas, J.B., Kumar, R.S.S., Perera, S.A., Chan, A.S.Y., Kobakhidze, N., George, R., Vijaya, L., Do, T., Edward, D.P., Juan Marcos, L. de, Pakravan, M., Moghimi, S., Ideta, R., Bach-Holm, D., Kappelgaard, P., Wirostko, B., Thomas, S., Gaston, D., Bedard, K., Greer, W.L., Yang, Z, Chen, X., Huang, L., Sang, J., Jia, H., Jia, L., Qiao, C., Zhang, H., Liu, X., Zhao, B., Wang, Y.X., Xu, L., Leruez, S., Reynier, P., Chichua, G., Tabagari, S., Uebe, S., Zenkel, M., Berner, D., Mossbock, G., Weisschuh, N., Hoja, U., Welge-Luessen, U.C., Mardin, C., Founti, P., Chatzikyriakidou, A., Pappas, T., Anastasopoulos, E., Lambropoulos, A., Ghosh, A., Shetty, R., Porporato, N., Saravanan, V., Venkatesh, R., Shivkumar, C., Kalpana, N., Sarangapani, S., Kanavi, M.R., Beni, A.N., Yazdani, S., Hollander, A.I. den, Pasutto, F., Khor, C.C., Aung, T., Ozaki, M., Lee, M.C., Schlotzer-Schrehardt, U., Thorleifsson, G., Mizoguchi, T., Igo, R.P., Jr., Haripriya, A., Williams, S.E., Astakhov, Y.S., Orr, A.C., Burdon, K.P., Nakano, S., Mori, K., Abu-Amero, K., Hauser, M., Li, Z., Prakadeeswari, G., Bailey, J.N., Cherecheanu, A.P., Kang, J.H., Nelson, S., Hayashi, K., Manabe, S.I., Kazama, S., Zarnowski, T., Inoue, K., Irkec, M., Coca-Prados, M., Sugiyama, K., Jarvela, I., Schlottmann, P., Lerner, S.F., Lamari, H., Nilgun, Y., Bikbov, M., Park, K.H., Cha, S.C., Yamashiro, K., Zenteno, J.C., Jonas, J.B., Kumar, R.S.S., Perera, S.A., Chan, A.S.Y., Kobakhidze, N., George, R., Vijaya, L., Do, T., Edward, D.P., Juan Marcos, L. de, Pakravan, M., Moghimi, S., Ideta, R., Bach-Holm, D., Kappelgaard, P., Wirostko, B., Thomas, S., Gaston, D., Bedard, K., Greer, W.L., Yang, Z, Chen, X., Huang, L., Sang, J., Jia, H., Jia, L., Qiao, C., Zhang, H., Liu, X., Zhao, B., Wang, Y.X., Xu, L., Leruez, S., Reynier, P., Chichua, G., Tabagari, S., Uebe, S., Zenkel, M., Berner, D., Mossbock, G., Weisschuh, N., Hoja, U., Welge-Luessen, U.C., Mardin, C., Founti, P., Chatzikyriakidou, A., Pappas, T., Anastasopoulos, E., Lambropoulos, A., Ghosh, A., Shetty, R., Porporato, N., Saravanan, V., Venkatesh, R., Shivkumar, C., Kalpana, N., Sarangapani, S., Kanavi, M.R., Beni, A.N., Yazdani, S., Hollander, A.I. den, Pasutto, F., and Khor, C.C.
- Abstract
Item does not contain fulltext, Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
- Published
- 2017