IGLESIAS, A. I.; MISHRA, Aniket; VITART, V.; BYKHOVSKAYA, Y.; HOHN, R.; SPRINGELKAMP, H.; CUELLAR-PARTIDA, G.; GHARAHKHANI, P.; BAILEY, J. N. C.; WILLOUGHBY, C. E.; LI, X.; YAZAR, S.; NAG, A.; KHAWAJA, A. P.; POLASEK, O.; SISCOVICK, D.; MITCHELL, P.; THAM, Y. C.; HAINES, J. L.; KEARNS, L. S.; HAYWARD, C.; SHI, Y.; VAN LEEUWEN, E. M.; TAYLOR, K. D.; BONNEMAIJER, P.; ROTTER, J. I.; MARTIN, N. G.; ZELLER, T.; MILLS, R. A.; STAFFIERI, S. E.; JONAS, J. B.; SCHMIDTMANN, I.; BOUTIN, T.; KANG, J. H.; LUCAS, S. E. M.; WONG, T. Y.; BEUTEL, M. E.; WILSON, J. F.; UITTERLINDEN, A. G.; VITHANA, E. N.; FOSTER, P. J.; HYSI, P. G.; HEWITT, A. W.; KHOR, C. C.; PASQUALE, L. R.; MONTGOMERY, G. W.; KLAVER, C. C. W.; AUNG, T.; PFEIFFER, N.; MACKEY, D. A.; HAMMOND, C. J.; CHENG, C. Y.; CRAIG, J. E.; RABINOWITZ, Y. S.; WIGGS, J. L.; BURDON, K. P.; VAN DUIJN, C. M.; MACGREGOR, S.

doi:10.1038/s41467-018-03646-6

Bordeaux population health [BPH]

VITART, V.

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Article de revue

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Nature Communications. 2018-05-14, vol. 9, n° 1, p. 1864

Résumé en anglais

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 x 10(-5)) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/14062

DOI

http://dx.doi.org/10.1038/s41467-018-03646-6

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

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Mots clés en anglais

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