Abstract
Original language | English |
---|---|
Article number | 1864 |
Journal | Nature communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2018 |
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In: Nature communications, Vol. 9, No. 1, 1864, 2018.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
AU - Iglesias, Adriana I.
AU - Mishra, Aniket
AU - Vitart, Veronique
AU - Bykhovskaya, Yelena
AU - Höhn, René
AU - Springelkamp, Henriët
AU - Cuellar-Partida, Gabriel
AU - Gharahkhani, Puya
AU - Bailey, Jessica N. Cooke
AU - Willoughby, Colin E.
AU - Li, Xiaohui
AU - Yazar, Seyhan
AU - Nag, Abhishek
AU - Khawaja, Anthony P.
AU - Polašek, Ozren
AU - Siscovick, David
AU - Mitchell, Paul
AU - Tham, Yih Chung
AU - Haines, Jonathan L.
AU - Kearns, Lisa S.
AU - Hayward, Caroline
AU - Shi, Yuan
AU - van Leeuwen, Elisabeth M.
AU - Taylor, Kent D.
AU - Wang, Jie Jin
AU - Rochtchina, Elena
AU - Attia, John
AU - Scott, Rodney
AU - Holliday, Elizabeth G.
AU - Baird, Paul N.
AU - Xie, Jing
AU - Inouye, Michael
AU - Viswanathan, Ananth
AU - Sim, Xueling
AU - Bonnemaijer, Pieter
AU - Rotter, Jerome I.
AU - Martin, Nicholas G.
AU - Zeller, Tanja
AU - Mills, Richard A.
AU - Staffieri, Sandra E.
AU - Jonas, Jost B.
AU - Schmidtmann, Irene
AU - Boutin, Thibaud
AU - Kang, Jae H.
AU - Lucas, Sionne E. M.
AU - Wong, Tien Yin
AU - Beutel, Manfred E.
AU - Wilson, James F.
AU - Allingham, R. Rand
AU - Brilliant, Murray H.
AU - Budenz, Donald L.
AU - Christen, William G.
AU - Fingert, John
AU - Friedman, David S.
AU - Gaasterland, Douglas
AU - Gaasterland, Terry
AU - Hauser, Michael A.
AU - Kraft, Peter
AU - Lee, Richard K.
AU - Lichter, Paul R.
AU - Liu, Yutao
AU - Loomis, Stephanie J.
AU - Moroi, Sayoko E.
AU - Pericak-Vance, Margaret A.
AU - Realini, Anthony
AU - Richards, Julia E.
AU - Schuman, Joel S.
AU - Scott, William K.
AU - Singh, Kuldev
AU - Sit, Arthur J.
AU - Vollrath, Douglas
AU - Weinreb, Robert N.
AU - Wollstein, Gadi
AU - Zack, Donald J.
AU - Zhang, Kang
AU - Donnelly, Peter
AU - Barroso, Ines
AU - Blackwell, Jenefer M.
AU - Bramon, Elvira
AU - Brown, Matthew A.
AU - Casas, Juan P.
AU - Corvin, Aiden
AU - Deloukas, Panos
AU - Duncanson, Audrey
AU - Jankowski, Janusz
AU - Markus, Hugh S.
AU - Mathew, Christopher G.
AU - Palmer, Colin N. A.
AU - Plomin, Robert
AU - Rautanen, Anna
AU - Sawcer, Stephen J.
AU - Trembath, Richard C.
AU - Wood, Nicholas W.
AU - Spencer, Chris C. A.
AU - Band, Gavin
AU - Bellenguez, C. line
AU - Freeman, Colin
AU - Hellenthal, Garrett
AU - Giannoulatou, Eleni
AU - Pirinen, Matti
AU - Pearson, Richard
AU - Strange, Amy
AU - Su, Zhan
AU - Vukcevic, Damjan
AU - Langford, Cordelia
AU - Hunt, Sarah E.
AU - Edkins, Sarah
AU - Gwilliam, Rhian
AU - Blackburn, Hannah
AU - Bumpstead, Suzannah J.
AU - Dronov, Serge
AU - Gillman, Matthew
AU - Gray, Emma
AU - Hammond, Naomi
AU - Jayakumar, Alagurevathi
AU - McCann, Owen T.
AU - Liddle, Jennifer
AU - Potter, Simon C.
AU - Ravindrarajah, Radhi
AU - Ricketts, Michelle
AU - Waller, Matthew
AU - Weston, Paul
AU - Widaa, Sara
AU - Whittaker, Pamela
AU - Uitterlinden, André G.
AU - Vithana, Eranga N.
AU - Foster, Paul J.
AU - Hysi, Pirro G.
AU - Hewitt, Alex W.
AU - Khor, Chiea Chuen
AU - Pasquale, Louis R.
AU - Montgomery, Grant W.
AU - Klaver, Caroline C. W.
AU - Aung, Tin
AU - Pfeiffer, Norbert
AU - MacKey, David A.
AU - Hammond, Christopher J.
AU - Cheng, Ching-Yu
AU - Craig, Jamie E.
AU - Rabinowitz, Yaron S.
AU - Wiggs, Janey L.
AU - Burdon, Kathryn P.
AU - van Duijn, Cornelia M.
AU - MacGregor, Stuart
PY - 2018
Y1 - 2018
N2 - 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 × 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.
AB - 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 × 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85047061045&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29760442
U2 - https://doi.org/10.1038/s41467-018-03646-6
DO - https://doi.org/10.1038/s41467-018-03646-6
M3 - Article
C2 - 29760442
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1864
ER -