Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23291589
TITLE
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
ABSTRACT
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.
DATE PUBLISHED
2013 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/05/01
accepted 2012/11/29
aheadofprint 2013/01/06
entrez 2013/01/08 06:00
pubmed 2013/01/08 06:00
medline 2013/03/27 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lu Y Lu Yi Y Queensland Institute of Medical Research, Statistical Genetics, Herston, Brisbane, Queensland, Australia.
Vitart V Vitart Veronique V
Burdon KP Burdon Kathryn P KP
Khor CC Khor Chiea Chuen CC
Bykhovskaya Y Bykhovskaya Yelena Y
Mirshahi A Mirshahi Alireza A
Hewitt AW Hewitt Alex W AW
Koehn D Koehn Demelza D
Hysi PG Hysi Pirro G PG
Ramdas WD Ramdas Wishal D WD
Zeller T Zeller Tanja T
Vithana EN Vithana Eranga N EN
Cornes BK Cornes Belinda K BK
Tay WT Tay Wan-Ting WT
Tai ES Tai E Shyong ES
Cheng CY Cheng Ching-Yu CY
Liu J Liu Jianjun J
Foo JN Foo Jia-Nee JN
Saw SM Saw Seang Mei SM
Thorleifsson G Thorleifsson Gudmar G
Stefansson K Stefansson Kari K
Dimasi DP Dimasi David P DP
Mills RA Mills Richard A RA
Mountain J Mountain Jenny J
Ang W Ang Wei W
Hoehn R Hoehn René R
Verhoeven VJ Verhoeven Virginie J M VJ
Grus F Grus Franz F
Wolfs R Wolfs Roger R
Castagne R Castagne Rapha√ęle R
Lackner KJ Lackner Karl J KJ
Springelkamp H Springelkamp Henri√ęt H
Yang J Yang Jian J
Jonasson F Jonasson Fridbert F
Leung DY Leung Dexter Y L DY
Chen LJ Chen Li J LJ
Tham CC Tham Clement C Y CC
Rudan I Rudan Igor I
Vatavuk Z Vatavuk Zoran Z
Hayward C Hayward Caroline C
Gibson J Gibson Jane J
Cree AJ Cree Angela J AJ
MacLeod A MacLeod Alex A
Ennis S Ennis Sarah S
Polasek O Polasek Ozren O
Campbell H Campbell Harry H
Wilson JF Wilson James F JF
Viswanathan AC Viswanathan Ananth C AC
Fleck B Fleck Brian B
Li X Li Xiaohui X
Siscovick D Siscovick David D
Taylor KD Taylor Kent D KD
Rotter JI Rotter Jerome I JI
Yazar S Yazar Seyhan S
Ulmer M Ulmer Megan M
Li J Li Jun J
Yaspan BL Yaspan Brian L BL
Ozel AB Ozel Ayse B AB
Richards JE Richards Julia E JE
Moroi SE Moroi Sayoko E SE
Haines JL Haines Jonathan L JL
Kang JH Kang Jae H JH
Pasquale LR Pasquale Louis R LR
Allingham RR Allingham R Rand RR
Ashley-Koch A Ashley-Koch Allison A
NEIGHBOR Consortium
Mitchell P Mitchell Paul P
Wang JJ Wang Jie Jin JJ
Wright AF Wright Alan F AF
Pennell C Pennell Craig C
Spector TD Spector Timothy D TD
Young TL Young Terri L TL
Klaver CC Klaver Caroline C W CC
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Anderson MG Anderson Michael G MG
Aung T Aung Tin T
Willoughby CE Willoughby Colin E CE
Wiggs JL Wiggs Janey L JL
Pang CP Pang Chi P CP
Thorsteinsdottir U Thorsteinsdottir Unnur U
Lotery AJ Lotery Andrew J AJ
Hammond CJ Hammond Christopher J CJ
van Duijn CM van Duijn Cornelia M CM
Hauser MA Hauser Michael A MA
Rabinowitz YS Rabinowitz Yaron S YS
Pfeiffer N Pfeiffer Norbert N
Mackey DA Mackey David A DA
Craig JE Craig Jamie E JE
Macgregor S Macgregor Stuart S
Wong TY Wong Tien Y TY
INVESTIGATORS
JOURNAL
VOLUME: 45
ISSUE: 2
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2013
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
CZB/4/710 Chief Scientist Office United Kingdom
F32 EY021436 NEI NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
R01 EY018246 NEI NIH HHS United States
R01 EY018825 NEI NIH HHS United States
R01 EY022305 NEI NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Asian Continental Ancestry Group genetics
Cornea anatomy & histology
Corneal Pachymetry anatomy & histology
European Continental Ancestry Group genetics
Fibronectins genetics
Forkhead Transcription Factors genetics
Genetic Loci genetics
Genome-Wide Association Study genetics
Glaucoma genetics
Humans genetics
Keratoconus genetics
Microarray Analysis genetics
Odds Ratio genetics
Real-Time Polymerase Chain Reaction genetics
SUPPLEMENTARY MESH
SUPPLMESHNAME SUPPLMESHTYPE
Glaucoma 1, Open Angle, O Disease
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 FNDC3B protein, human
0 FOXO1 protein, human
0 Fibronectins
0 Forkhead Transcription Factors
OTHER ID's
OTHERID SOURCE
NIHMS479022 NLM
PMC3720123 NLM