Genetic Epidemiology, Psychiatric Genetics, Asthma 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
27174397
TITLE
Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.
ABSTRACT
NlmCategory: UNASSIGNED
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
DATE PUBLISHED
2016
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/02/10
accepted 2016/04/25
entrez 2016/05/14 06:00
pubmed 2016/05/14 06:00
medline 2016/05/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Fan Q Fan Qiao Q Centre for Quantitative Medicine, Duke-NUS Medial School, Singapore.
Guo X Guo Xiaobo X State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Tideman JW Tideman J Willem L JW Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Williams KM Williams Katie M KM Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.
Yazar S Yazar Seyhan S Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
Hosseini SM Hosseini S Mohsen SM Genetics and Genome Biology Program, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Howe LD Howe Laura D LD School of Social and Community Medicine, University of Bristol, Bristol, UK.
Pourcain BS Pourcain Beaté St BS Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD Nijmegen, The Netherlands.
Evans DM Evans David M DM University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
Timpson NJ Timpson Nicholas J NJ MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
McMahon G McMahon George G MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
Hysi PG Hysi Pirro G PG Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.
Krapohl E Krapohl Eva E MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.
Wang YX Wang Ya Xing YX Beijing Ophthalmology and Visual Science Key Lab, Beijing, China.
Jonas JB Jonas Jost B JB Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
Baird PN Baird Paul Nigel PN Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Wang JJ Wang Jie Jin JJ Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.
Cheng CY Cheng Ching-Yu CY Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Teo YY Teo Yik-Ying YY Saw Swee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore, Singapore.
Wong TY Wong Tien-Yin TY Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Ding X Ding Xiaohu X State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Wojciechowski R Wojciechowski Robert R Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD.
Young TL Young Terri L TL Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
Pärssinen O Pärssinen Olavi O Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland.
Oexle K Oexle Konrad K Institute of Human Genetics, Technical University Munich, Munich, Germany.
Pfeiffer N Pfeiffer Norbert N Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
Bailey-Wilson JE Bailey-Wilson Joan E JE Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA.
Paterson AD Paterson Andrew D AD Genetics and Genome Biology Program, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Klaver CC Klaver Caroline C W CC Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Plomin R Plomin Robert R MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.
Hammond CJ Hammond Christopher J CJ Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.
Mackey DA Mackey David A DA Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
He M He Mingguang M Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Saw SM Saw Seang-Mei SM Saw Swee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore, Singapore.
Williams C Williams Cathy C School of Social and Community Medicine, University of Bristol, Bristol, UK.
Guggenheim JA Guggenheim Jeremy A JA School of Optometry &Vision Sciences, Cardiff University, Cardiff, UK.
CREAM Consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Meguro Akira A
Wright Alan F AF
Hewitt Alex W AW
Young Alvin L AL
Veluchamy Amutha Barathi AB
Metspalu Andres A
Paterson Andrew D AD
Döring Angela A
Khawaja Anthony P AP
Klein Barbara E BE
Pourcain Beate St BS
Fleck Brian B
Klaver Caroline C W CC
Hayward Caroline C
Williams Cathy C
Delcourt Cécile C
Pang Chi Pui CP
Khor Chiea-Chuen CC
Cheng Ching-Yu CY
Gieger Christian C
Hammond Christopher J CJ
Simpson Claire L CL
van Duijn Cornelia M CM
Mackey David A DA
Evans David M DM
Stambolian Dwight D
Chew Emily E
Tai E-Shyong ES
Krapohl Eva E
Mihailov Evelin E
Smith George Davey GD
McMahon George G
Biino Ginevra G
Campbell Harry H
Rudan Igor I
Seppälä Ilkka I
Kaprio Jaakko J
Wilson James F JF
Craig Jamie E JE
Tideman J Willem L JW
Ried Janina S JS
Korobelnik Jean-François JF
Guggenheim Jeremy A JA
Fondran Jeremy R JR
Wang Jie Jin JJ
Liao Jiemin J
Zhao Jing Hua JH
Xie Jing J
Bailey-Wilson Joan E JE
Kemp John P JP
Lass Jonathan H JH
Jonas Jost B JB
Rahi Jugnoo S JS
Wedenoja Juho J
Mäkelä Kari-Matti KM
Burdon Kathryn P KP
Williams Katie M KM
Khaw Kay-Tee KT
Yamashiro Kenji K
Oexle Konrad K
Howe Laura D LD
Chen Li Jia LJ
Xu Liang L
Farrer Lindsay L
Ikram M Kamran MK
Deangelis Margaret M MM
Morrison Margaux M
Schache Maria M
Pirastu Mario M
Miyake Masahiro M
Yap Maurice K H MK
Fossarello Maurizio M
Kähönen Mika M
Tedja Milly S MS
He Mingguang M
Yoshimura Nagahisa N
Martin Nicholas G NG
Timpson Nicholas J NJ
Wareham Nick J NJ
Mizuki Nobuhisa N
Pfeiffer Norbert N
Pärssinen Olavi O
Raitakari Olli O
Polasek Ozren O
Tam Pancy O PO
Foster Paul J PJ
Mitchell Paul P
Baird Paul Nigel PN
Chen Peng P
Hysi Pirro G PG
Cumberland Phillippa P
Gharahkhani Puya P
Fan Qiao Q
Höhn René R
Fogarty Rhys D RD
Luben Robert N RN
Igo Jr Robert P RP
Plomin Robert R
Wojciechowski Robert R
Klein Ronald R
Mohsen Hosseini S S
Janmahasatian Sarayut S
Saw Seang-Mei SM
Yazar Seyhan S
Ping Yip Shea S
Feng Sheng S
Vaccargiu Simona S
Panda-Jonas Songhomitra S
MacGregor Stuart S
Iyengar Sudha K SK
Rantanen Taina T
Lehtimäki Terho T
Young Terri L TL
Meitinger Thomas T
Wong Tien-Yin TY
Aung Tin T
Haller Toomas T
Vitart Veronique V
Nangia Vinay V
Verhoeven Virginie J M VJ
Jhanji Vishal V
Zhao Wanting W
Chen Wei W
Zhou Xiangtian X
Guo Xiaobo X
Ding Xiaohu X
Wang Ya Xing YX
Lu Yi Y
Teo Yik-Ying YY
Vatavuk Zoran Z
JOURNAL
VOLUME: 6
ISSUE:
TITLE: Scientific reports
ISOABBREVIATION: Sci Rep
YEAR:
MONTH:
DAY:
MEDLINEDATE: 2016
SEASON:
CITEDMEDIUM: Internet
ISSN: 2045-2322
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Sci Rep
COUNTRY: England
ISSNLINKING: 2045-2322
NLMUNIQUEID: 101563288
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