Document Detail


Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
MedLine Citation:
PMID:  23291589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
Authors:
Yi Lu; Veronique Vitart; Kathryn P Burdon; Chiea Chuen Khor; Yelena Bykhovskaya; Alireza Mirshahi; Alex W Hewitt; Demelza Koehn; Pirro G Hysi; Wishal D Ramdas; Tanja Zeller; Eranga N Vithana; Belinda K Cornes; Wan-Ting Tay; E Shyong Tai; Ching-Yu Cheng; Jianjun Liu; Jia-Nee Foo; Seang Mei Saw; Gudmar Thorleifsson; Kari Stefansson; David P Dimasi; Richard A Mills; Jenny Mountain; Wei Ang; René Hoehn; Virginie J M Verhoeven; Franz Grus; Roger Wolfs; Raphaële Castagne; Karl J Lackner; Henriët Springelkamp; Jian Yang; Fridbert Jonasson; Dexter Y L Leung; Li J Chen; Clement C Y Tham; Igor Rudan; Zoran Vatavuk; Caroline Hayward; Jane Gibson; Angela J Cree; Alex MacLeod; Sarah Ennis; Ozren Polasek; Harry Campbell; James F Wilson; Ananth C Viswanathan; Brian Fleck; Xiaohui Li; David Siscovick; Kent D Taylor; Jerome I Rotter; Seyhan Yazar; Megan Ulmer; Jun Li; Brian L Yaspan; Ayse B Ozel; Julia E Richards; Sayoko E Moroi; Jonathan L Haines; Jae H Kang; Louis R Pasquale; R Rand Allingham; Allison Ashley-Koch; ; Paul Mitchell; Jie Jin Wang; Alan F Wright; Craig Pennell; Timothy D Spector; Terri L Young; Caroline C W Klaver; Nicholas G Martin; Grant W Montgomery; Michael G Anderson; Tin Aung; Colin E Willoughby; Janey L Wiggs; Chi P Pang; Unnur Thorsteinsdottir; Andrew J Lotery; Christopher J Hammond; Cornelia M van Duijn; Michael A Hauser; Yaron S Rabinowitz; Norbert Pfeiffer; David A Mackey; Jamie E Craig; Stuart Macgregor; Tien Y Wong
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Publication Detail:
Type:  Journal Article; Meta-Analysis     Date:  2013-01-06
Journal Detail:
Title:  Nature genetics     Volume:  45     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-03-26     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Asian Continental Ancestry Group / genetics
Cornea / anatomy & histology*
Corneal Pachymetry
European Continental Ancestry Group / genetics
Fibronectins / genetics*
Forkhead Transcription Factors / genetics*
Genetic Loci / genetics*
Genome-Wide Association Study
Glaucoma / genetics
Humans
Keratoconus / genetics*
Microarray Analysis
Odds Ratio
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
CZB/4/710//Chief Scientist Office; F32 EY021436/EY/NEI NIH HHS; MC_PC_U127561128//Medical Research Council; R01 EY018246/EY/NEI NIH HHS; R01 EY018825/EY/NEI NIH HHS; R01 EY022305/EY/NEI NIH HHS; UL1 TR000124/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/FNDC3B protein, human; 0/FOXO1 protein, human; 0/Fibronectins; 0/Forkhead Transcription Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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