@article{958fbf19c0924351bae27aa2cbae0eda,
title = "Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy",
abstract = "The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10 -'8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.",
author = "Afshari, {Natalie A.} and Igo, {Robert P.} and Morris, {Nathan J.} and Dwight Stambolian and Shiwani Sharma and Pulagam, {V. Lakshmi} and Steven Dunn and Stamler, {John F.} and Truitt, {Barbara J.} and Jacqueline Rimmler and Abraham Kuot and Croasdale, {Christopher R.} and Xuejun Qin and Burdon, {Kathryn P.} and Riazuddin, {S. Amer} and Richard Mills and Sonja Klebe and Minear, {Mollie A.} and Jiagang Zhao and Elmer Balajonda and Rosenwasser, {George O.} and Baratz, {Keith H.} and Mootha, {V. Vinod} and Patel, {Sanjay V.} and Gregory, {Simon G.} and Bailey-Wilson, {Joan E.} and Price, {Marianne O.} and Price, {Francis W.} and Craig, {Jamie E.} and Fingert, {John H.} and Gottsch, {John D.} and Aldave, {Anthony J.} and Klintworth, {Gordon K.} and Lass, {Jonathan H.} and Li, {Yi Ju} and Iyengar, {Sudha K.}",
note = "Funding Information: We would like to acknowledge the strong scientific know-how and mentorship provided by Dr Gordon Klintworth, who passed away during the writing of this paper.We are incredibly grateful for the wisdom he imparted. We are also grateful to the patients who provided us with information and samples, and made this study possible. Finally, we would like to show appreciation to the many funding agencies who supported this research, including National Eye Institute Grants R01 EY023196, R01 EY016482, R01 EY016514, R01 EY016835, R21 EY015145 and P30 EY11373; Research to Prevent Blindness; the Beulah and Florence Usher Endowment; NHMRC (Australia) Grant No 1031362; Ophthalmic Research Institute of Australia; Flinders Medical Centre Foundation; the Ohio Lions Eye Research Foundation; and the intramural research program of the National Human Genome Research Institute, National Institutes of Health (NIH). Genotyping was performed by the Centre for Inherited Disease Research under Grant 1X01HG006619. This publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, 4UL1TR000439, from the National Centre for Advancing Translational Sciences (NCATS) component of the NIH and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This article was prepared while M.A.M. was employed at Duke University; she is currently serving as an American Association for the Advancement of Science (AAAS) Science & Technology Policy Fellow at the NIH. She worked on this article in her personal capacity, and the opinions expressed in this article are her own and do not necessarily reflect the views of the NIH, the Department of Health and Human Services or the United States government.",
year = "2017",
month = mar,
day = "30",
doi = "10.1038/ncomms14898",
language = "English (US)",
volume = "8",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}