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
23396134
TITLE
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.
ABSTRACT
Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.
DATE PUBLISHED
2013 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/10/03
accepted 2013/01/16
aheadofprint 2013/02/10
entrez 2013/02/12 06:00
pubmed 2013/02/12 06:00
medline 2013/06/01 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Verhoeven VJ Verhoeven Virginie J M VJ Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Hysi PG Hysi Pirro G PG
Wojciechowski R Wojciechowski Robert R
Fan Q Fan Qiao Q
Guggenheim JA Guggenheim Jeremy A JA
Höhn R Höhn René R
MacGregor S MacGregor Stuart S
Hewitt AW Hewitt Alex W AW
Nag A Nag Abhishek A
Cheng CY Cheng Ching-Yu CY
Yonova-Doing E Yonova-Doing Ekaterina E
Zhou X Zhou Xin X
Ikram MK Ikram M Kamran MK
Buitendijk GH Buitendijk Gabriëlle H S GH
McMahon G McMahon George G
Kemp JP Kemp John P JP
Pourcain BS Pourcain Beate St BS
Simpson CL Simpson Claire L CL
Mäkelä KM Mäkelä Kari-Matti KM
Lehtimäki T Lehtimäki Terho T
Kähönen M Kähönen Mika M
Paterson AD Paterson Andrew D AD
Hosseini SM Hosseini S Mohsen SM
Wong HS Wong Hoi Suen HS
Xu L Xu Liang L
Jonas JB Jonas Jost B JB
Pärssinen O Pärssinen Olavi O
Wedenoja J Wedenoja Juho J
Yip SP Yip Shea Ping SP
Ho DW Ho Daniel W H DW
Pang CP Pang Chi Pui CP
Chen LJ Chen Li Jia LJ
Burdon KP Burdon Kathryn P KP
Craig JE Craig Jamie E JE
Klein BE Klein Barbara E K BE
Klein R Klein Ronald R
Haller T Haller Toomas T
Metspalu A Metspalu Andres A
Khor CC Khor Chiea-Chuen CC
Tai ES Tai E-Shyong ES
Aung T Aung Tin T
Vithana E Vithana Eranga E
Tay WT Tay Wan-Ting WT
Barathi VA Barathi Veluchamy A VA
Consortium for Refractive Error and Myopia (CREAM)
Chen P Chen Peng P
Li R Li Ruoying R
Liao J Liao Jiemin J
Zheng Y Zheng Yingfeng Y
Ong RT Ong Rick T RT
Döring A Döring Angela A
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group
Evans DM Evans David M DM
Timpson NJ Timpson Nicholas J NJ
Verkerk AJ Verkerk Annemieke J M H AJ
Meitinger T Meitinger Thomas T
Raitakari O Raitakari Olli O
Hawthorne F Hawthorne Felicia F
Spector TD Spector Tim D TD
Karssen LC Karssen Lennart C LC
Pirastu M Pirastu Mario M
Murgia F Murgia Federico F
Ang W Ang Wei W
Wellcome Trust Case Control Consortium 2 (WTCCC2)
Mishra A Mishra Aniket A
Montgomery GW Montgomery Grant W GW
Pennell CE Pennell Craig E CE
Cumberland PM Cumberland Phillippa M PM
Cotlarciuc I Cotlarciuc Ioana I
Mitchell P Mitchell Paul P
Wang JJ Wang Jie Jin JJ
Schache M Schache Maria M
Janmahasatian S Janmahasatian Sarayut S
Janmahasathian S Janmahasathian Sarayut S
Igo RP Jr Igo Robert P RP
Lass JH Lass Jonathan H JH
Chew E Chew Emily E
Iyengar SK Iyengar Sudha K SK
Fuchs' Genetics Multi-Center Study Group
Gorgels TG Gorgels Theo G M F TG
Rudan I Rudan Igor I
Hayward C Hayward Caroline C
Wright AF Wright Alan F AF
Polasek O Polasek Ozren O
Vatavuk Z Vatavuk Zoran Z
Wilson JF Wilson James F JF
Fleck B Fleck Brian B
Zeller T Zeller Tanja T
Mirshahi A Mirshahi Alireza A
Müller C Müller Christian C
Uitterlinden AG Uitterlinden André G AG
Rivadeneira F Rivadeneira Fernando F
Vingerling JR Vingerling Johannes R JR
Hofman A Hofman Albert A
Oostra BA Oostra Ben A BA
Amin N Amin Najaf N
Bergen AA Bergen Arthur A B AA
Teo YY Teo Yik-Ying YY
Rahi JS Rahi Jugnoo S JS
Vitart V Vitart Veronique V
Williams C Williams Cathy C
Baird PN Baird Paul N PN
Wong TY Wong Tien-Yin TY
Oexle K Oexle Konrad K
Pfeiffer N Pfeiffer Norbert N
Mackey DA Mackey David A DA
Young TL Young Terri L TL
van Duijn CM van Duijn Cornelia M CM
Saw SM Saw Seang-Mei SM
Bailey-Wilson JE Bailey-Wilson Joan E JE
Stambolian D Stambolian Dwight D
Klaver CC Klaver Caroline C CC
Hammond CJ Hammond Christopher J CJ
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Rahi Jugnoo S JS
Hysi Pirro G PG
Yoshimura Nagahisa N
Yamashiro Kenji K
Miyake Masahiro M
Delcourt Cécile C
Maubaret Cecilia C
Williams Cathy C
Guggenheim Jeremy A JA
Northstone Kate K
Ring Susan M SM
Craig Jamie E JE
Burdon Kathryn P KP
Fogarty Rhys D RD
Iyengar Sudha K SK
Igo Robert P RP
Chew Emily E
Janmahasathian Sarayut S
Iyengar Sudha K SK
Stambolian Dwight D
Wilson Joan E Bailey JE
MacGregor Stuart S
Lu Yi Y
Jonas Jost B JB
Xu Liang L
Baird Paul N PN
Rochtchina Elena E
Mitchell Paul P
Wang Jie Jin JJ
Jonas Jost B JB
Nangia Vinay V
Hayward Caroline C
Wright Alan F AF
Vitart Veronique V
Polasek Ozren O
Campbell Harry H
Vitart Veronique V
Rudan Igor I
Vatavuk Zoran Z
Vitart Veronique V
Paterson Andrew D AD
Hosseini S Mohsen S
Iyengar Sudha K SK
Fondran Jeremy R JR
Young Terri L TL
Feng Sheng S
Verhoeven Virginie J M VJ
Klaver Caroline C CC
van Duijn Cornelia M CM
Metspalu Andres A
Haller Toomas T
Mihailov Evelin E
Pärssinen Olavi O
Wilson Juho Wedenoja Joan E Bailey JW
Wojciechowski Robert R
Baird Paul N PN
Schache Maria M
Pfeiffer Norbert N
Höhn René R
Pang Chi Pui CP
Chen Peng P
Meitinger Thomas T
Oexle Konrad K
Wegner Aharon A
Yoshimura Nagahisa N
Yamashiro Kenji K
Miyak Masahiro M
Pärssinen Olavi O
Yip Shea Ping SP
Ho Daniel W H DW
Pirastu Mario M
Murgia Federico F
Portas Laura L
Biino Genevra G
Wilson James F JF
Fleck Brian B
Vitart Veronique V
Stambolian Dwight D
Wilson Joan E Bailey JE
Hewitt Alex W AW
Ang Wei W
Verhoeven Virginie J M VJ
Klaver Caroline C CC
van Duijn Cornelia M CM
Zhou Xin X
Ikram M Kamran M
Fan Qiao Q
Zhou Xin X
Mackey M Kamran David A M
MacGregor Stuart S
Hammond Christopher J CJ
Hysi Pirro G PG
Deangelis Margaret M MM
Morrison Margaux M
Zhou Xiangtian X
Chen Wei W
Paterson Andrew D AD
Hosseini S Mohsen S
Mizuki Nobuhisa N
Meguro Akira A
Raitakari Olli O
Kähönen Mika M
Donnelly Peter P
Barroso Ines I
Blackwell Jenefer M JM
Bramon Elvira E
Brown Matthew A MA
Casas Juan P JP
Corvin Aiden A
Deloukas Panos P
Duncanson Audrey A
Jankowski Janusz J
Markus Hugh S HS
Mathew Christopher G CG
Palmer Colin N A CN
Plomin Robert R
Rautanen Anna A
Sawcer Stephen J SJ
Trembath Richard C RC
Viswanathan Ananth C AC
Wood Nicholas W NW
Spencer Chris C A CC
Band Gavin G
Bellenguez Céline C
Freeman Colin C
Hellenthal Garrett G
Giannoulatou Eleni E
Pirinen Matti M
Pearson Richard R
Strange Amy A
Su Zhan Z
Vukcevic Damjan D
Langford Cordelia C
Hunt Sarah E SE
Edkins Sarah S
Gwilliam Rhian R
Blackburn Hannah H
Bumpstead Suzannah J SJ
Dronov Serge S
Gillman Matthew M
Gray Emma E
Hammond Naomi N
Jayakumar Alagurevathi A
McCann Owen T OT
Liddle Jennifer J
Potter Simon C SC
Ravindrarajah Radhi R
Ricketts Michelle M
Waller Matthew M
Weston Paul P
Widaa Sara S
Whittaker Pamela P
Genuth S S
Nathan D M DM
Zinman B B
Crofford O O
Crandall J J
Reid M M
Engel S S
Sheindlin J J
Martinez H H
Shamoon H H
Engel H H
Phillips M M
Mayer L L
Pendegast S S
Zegarra H H
Miller D D
Singerman L L
Novak M M
Quin J J
Dahms W W
Genuth Saul S
Palmert M M
Brillon D D
Lackaye M E ME
Kiss S S
Chan R R
Reppucci V V
Lee T T
Heinemann M M
Whitehouse F F
Kruger D D
Jones J K J
McLellan M M
Carey J D JD
Angus E E
Thomas A A
Galprin A A
Bergenstal R R
Johnson M M
Spencer M M
Morgan K K
Aiello Lloyd Paul LP
Golden E E
Jacobson A A
Beaser R R
Ganda O O
Hamdy O O
Wolpert H H
Sharuk G G
Arrigg P P
Schlossman D D
Rosenzwieg J J
Nathan D M DM
Larkin M M
Ong M M
Godine J J
Cagliero E E
Lou P P
Folino K K
Fritz S S
Crowell S S
Hansen K K
Ziegler G G
Luttrell L L
Caulder S S
Colwell J J
Soule J J
Fernandes J J
Hermayer K K
Kwon S S
Brabham M M
Blevins A A
Parker J J
Lee D D
Patel N N
Pittman C C
Lindsey P P
Bracey M M
Lee K K
Nutaitis M M
Farr A A
Thompson T T
Selby J J
Lyons T T
Szpiech M M
Mayfield R R
Molitch M M
Schaefer B B
Jampol L L
Lyon A A
Gill M M
Strugula Z Z
Kaminski L L
Mirza R R
Simjanoski E E
Ryan D D
Kolterman O O
Lorenzi G G
Goldbaum M M
Sivitz W W
Bayless M M
Johnsonbaugh S S
Hebdon M M
Salemi P P
Liss R R
Donner T T
Gordon J J
Hemady R R
Kowarski A A
Ostrowski D D
Steidl S S
Jones B B
Herman W H WH
Martin C L CL
Sarma A A
Albers J J
Feldman E E
Kim K K
Elner S S
Comer G G
Gardner T T
Hackel R R
Prusak R R
Goings L L
Smith A A
Gothrup J J
Titus P P
Lee J J
Brandle M M
Prosser L L
Greene D A DA
Stevens M J MJ
Bantle J J
Wimmergren N N
Cochrane A A
Olsen T T
Steuer E E
Rath P P
Rogness B B
Hainsworth D D
Goldstein D D
Hitt S S
Giangiacomo J J
Canady J L JL
Chapin J E JE
Braunstein S S
Bourne P A PA
Schwartz S S
Brucker A A
Baker L L
Iyengar Sudha K SK
Lass Jonathan J
Reinhart William W
Belin Michael W MW
Schultze Robert L RL
Morason Todd T
Sugar Alan A
Mian Shahzad S
Soong Kaz Hunson KH
Colby Kathryn K
Yee Richard R
Vital Mark M
Alfonso Eduardo E
Karp Carol C
Lee Yunhee Y
Yoo Sonia S
Hammersmith Kristin K
Cohen Elisabeth E
Laibson Peter P
Rapuano Christopher C
Ayres Brandon B
Croasdale Christopher C
Caudill James J
Patel Sanjay S
Baratz Keith K
Bourne William W
Maguire Leo L
Sugar Joel J
Tu Elmer E
Djalilian Ali A
Mootha Vinod V
McCulley James J
Bowman Wayne W
Cavanaugh H Dwight H
Verity Steven S
Verdier David D
Renucci Ann A
Oliva Matt M
Rotkis Walter W
Hardten David R DR
Fahmy Ahmad A
Brown Marlene M
Reeves Sherman S
Davis Elizabeth A EA
Lindstrom Richard R
Hauswirth Scott S
Hamilton Stephen S
Lee W Barry W
Price Francis F
Price Marianne M
Kelly Kathleen K
Peters Faye F
Shaughnessy Michael M
Steinemann Thomas T
Dupps B J B
Meisler David M DM
Mifflin Mark M
Olson Randal R
Aldave Anthony A
Holland Gary G
Mondino Bartly J BJ
Rosenwasser George G
Gorovoy Mark M
Dunn Steven P SP
Heidemann David G DG
Terry Mark M
Shamie Neda N
Rosenfeld Steven I SI
Suedekum Brandon B
Hwang David D
Stone Donald D
Chodosh James J
Galentine Paul G PG
Bardenstein David D
Goddard Katrina K
Chin Hemin H
Mannis Mark M
Varma Rohit R
Borecki Ingrid I
Davey-Smith George G
Saw Seang-Mei SM
Wong Tien-Yin TY
Teo Yik-Ying YY
Cheng Ching-Yu CY
Lehtimäki Terho T
Mäkelä Kari-Matti KM
Brown-Friday J J
Gubitosi-Klug R R
Smith-Brewer S S
Etzwiler D D
Rand L L
Gauthier-Kelly C C
Service J J
Lopes-Virella M M
Elsing S S
Yacoub-Wasef S S
Wood D D
Counts D D
Pop-Busui R R
Vine A K AK
Schade D S DS
Ketai C L H LH
Maschak-Carey B J BJ
Jurkunas Ula U
JOURNAL
VOLUME: 45
ISSUE: 3
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2013
MONTH: Mar
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
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn Nat Genet. 2013 Jun;45(2):712 15266624 Janmahasathian, Sarayut [corrected to Sarayut Janmahasatian]
GRANTS
GRANTID AGENCY COUNTRY
076113 Wellcome Trust United Kingdom
076467 Wellcome Trust United Kingdom
083478 Wellcome Trust United Kingdom
08547508Z Wellcome Trust United Kingdom
085475B08Z Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
092731 Wellcome Trust United Kingdom
1K08EY022943-01 NEI NIH HHS United States
1R01EY018246 NEI NIH HHS United States
4882 Medical Research Council United Kingdom
CDF-2009-02-35 Department of Health United Kingdom
CZB/4/438 Chief Scientist Office United Kingdom
CZB/4/710 Chief Scientist Office United Kingdom
EY016379 NEI NIH HHS United States
G9815508 Medical Research Council United Kingdom
K08 EY022943 NEI NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U127584475 Medical Research Council United Kingdom
N01 DK062204 NIDDK NIH HHS United States
N01 DK062204-A NIDDK NIH HHS United States
N01EY22112 NEI NIH HHS United States
N01EY92109 NEI NIH HHS United States
N01HC25195 NHLBI NIH HHS United States
N01-DK-6-2204 NIDDK NIH HHS United States
N02HL64278 NHLBI NIH HHS United States
P30 EY014800 NEI NIH HHS United States
P30EY11373 NEI NIH HHS United States
R01 DK077510 NIDDK NIH HHS United States
R01 DK-077510 NIDDK NIH HHS United States
R01 EY018246 NEI NIH HHS United States
R01 EY020483 NEI NIH HHS United States
R01 EY020483 NEI NIH HHS United States
R01 EY023196 NEI NIH HHS United States
R01EY01824601 NEI NIH HHS United States
R01EY020483 NEI NIH HHS United States
R01EY03083 NEI NIH HHS United States
R01EY16482 NEI NIH HHS United States
R21EY015145 NEI NIH HHS United States
SRF/01/010 Department of Health United Kingdom
UL1 TR000041 NCATS NIH HHS United States
WT083431MA Wellcome Trust United Kingdom
Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alcohol Oxidoreductases genetics
Asian Continental Ancestry Group genetics
Bone Morphogenetic Protein 2 genetics
European Continental Ancestry Group genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Homeodomain Proteins genetics
Humans genetics
KCNQ Potassium Channels genetics
Laminin genetics
Myopia genetics
Receptors, AMPA genetics
Refractive Errors genetics
Risk Factors genetics
Serine Proteases genetics
Trans-Activators genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 BMP2 protein, human
0 Bone Morphogenetic Protein 2
0 Homeodomain Proteins
0 KCNQ Potassium Channels
0 KCNQ5 protein, human
0 Laminin
0 Receptors, AMPA
0 SIX6 protein, human
0 Trans-Activators
0 glutamate receptor ionotropic, AMPA 4
0 laminin alpha 2
EC 1.1.- Alcohol Oxidoreductases
EC 1.1.1.105 retinol dehydrogenase 5
EC 3.4.- PRSS56 protein, human
EC 3.4.- Serine Proteases
OTHER ID's
OTHERID SOURCE
NIHMS490585 NLM
PMC3740568 NLM
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