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| PMID |
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| TITLE |
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| Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. |
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| ABSTRACT |
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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). |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| AUTHORS |
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| 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 |
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State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. |
| Tideman JW |
|
Tideman |
J Willem L |
JW |
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Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. |
| Williams KM |
|
Williams |
Katie M |
KM |
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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 |
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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 |
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Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK. |
| Krapohl E |
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Krapohl |
Eva |
E |
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MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK. |
| Wang YX |
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Wang |
Ya Xing |
YX |
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Beijing Ophthalmology and Visual Science Key Lab, Beijing, China. |
| Jonas JB |
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Jonas |
Jost B |
JB |
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Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany. |
| Baird PN |
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Baird |
Paul Nigel |
PN |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
| Wang JJ |
|
Wang |
Jie Jin |
JJ |
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Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, Australia. |
| Cheng CY |
|
Cheng |
Ching-Yu |
CY |
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Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. |
| Teo YY |
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Teo |
Yik-Ying |
YY |
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Saw Swee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore, Singapore. |
| Wong TY |
|
Wong |
Tien-Yin |
TY |
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Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. |
| Ding X |
|
Ding |
Xiaohu |
X |
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State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. |
| Wojciechowski R |
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Wojciechowski |
Robert |
R |
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Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD. |
| Young TL |
|
Young |
Terri L |
TL |
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Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. |
| Pärssinen O |
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Pärssinen |
Olavi |
O |
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Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland. |
| Oexle K |
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Oexle |
Konrad |
K |
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Institute of Human Genetics, Technical University Munich, Munich, Germany. |
| Pfeiffer N |
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Pfeiffer |
Norbert |
N |
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Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany. |
| Bailey-Wilson JE |
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Bailey-Wilson |
Joan E |
JE |
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Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA. |
| Paterson AD |
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Paterson |
Andrew D |
AD |
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Genetics and Genome Biology Program, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada. |
| Klaver CC |
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Klaver |
Caroline C W |
CC |
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Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. |
| Plomin R |
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Plomin |
Robert |
R |
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MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK. |
| Hammond CJ |
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Hammond |
Christopher J |
CJ |
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Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK. |
| Mackey DA |
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Mackey |
David A |
DA |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
| He M |
|
He |
Mingguang |
M |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
| Saw SM |
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Saw |
Seang-Mei |
SM |
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Saw Swee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore, Singapore. |
| Williams C |
|
Williams |
Cathy |
C |
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School of Social and Community Medicine, University of Bristol, Bristol, UK. |
| Guggenheim JA |
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Guggenheim |
Jeremy A |
JA |
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School of Optometry &Vision Sciences, Cardiff University, Cardiff, UK. |
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CREAM Consortium |
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| INVESTIGATORS |
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| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Meguro |
Akira |
A |
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| Wright |
Alan F |
AF |
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| Hewitt |
Alex W |
AW |
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| Young |
Alvin L |
AL |
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| Veluchamy |
Amutha Barathi |
AB |
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| Metspalu |
Andres |
A |
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| Paterson |
Andrew D |
AD |
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| Döring |
Angela |
A |
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| Khawaja |
Anthony P |
AP |
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| Klein |
Barbara E |
BE |
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| Pourcain |
Beate St |
BS |
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| Fleck |
Brian |
B |
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| Klaver |
Caroline C W |
CC |
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| Hayward |
Caroline |
C |
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| Williams |
Cathy |
C |
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| Delcourt |
Cécile |
C |
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| Pang |
Chi Pui |
CP |
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| Khor |
Chiea-Chuen |
CC |
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| Cheng |
Ching-Yu |
CY |
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| Gieger |
Christian |
C |
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| Hammond |
Christopher J |
CJ |
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| Simpson |
Claire L |
CL |
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| van Duijn |
Cornelia M |
CM |
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| Mackey |
David A |
DA |
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| Evans |
David M |
DM |
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| Stambolian |
Dwight |
D |
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| Chew |
Emily |
E |
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| Tai |
E-Shyong |
ES |
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| Krapohl |
Eva |
E |
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| Mihailov |
Evelin |
E |
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| Smith |
George Davey |
GD |
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| McMahon |
George |
G |
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| Biino |
Ginevra |
G |
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| Campbell |
Harry |
H |
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| Rudan |
Igor |
I |
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| Seppälä |
Ilkka |
I |
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| Kaprio |
Jaakko |
J |
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| Wilson |
James F |
JF |
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| Craig |
Jamie E |
JE |
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| Tideman |
J Willem L |
JW |
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| Ried |
Janina S |
JS |
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| Korobelnik |
Jean-François |
JF |
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| Guggenheim |
Jeremy A |
JA |
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| Fondran |
Jeremy R |
JR |
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| Wang |
Jie Jin |
JJ |
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| Liao |
Jiemin |
J |
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| Zhao |
Jing Hua |
JH |
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| Xie |
Jing |
J |
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| Bailey-Wilson |
Joan E |
JE |
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| Kemp |
John P |
JP |
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| Lass |
Jonathan H |
JH |
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| Jonas |
Jost B |
JB |
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| Rahi |
Jugnoo S |
JS |
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| Wedenoja |
Juho |
J |
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| Mäkelä |
Kari-Matti |
KM |
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| Burdon |
Kathryn P |
KP |
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| Williams |
Katie M |
KM |
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| Khaw |
Kay-Tee |
KT |
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| Yamashiro |
Kenji |
K |
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| Oexle |
Konrad |
K |
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| Howe |
Laura D |
LD |
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| Chen |
Li Jia |
LJ |
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| Xu |
Liang |
L |
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| Farrer |
Lindsay |
L |
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| Ikram |
M Kamran |
MK |
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| Deangelis |
Margaret M |
MM |
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| Morrison |
Margaux |
M |
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| Schache |
Maria |
M |
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| Pirastu |
Mario |
M |
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| Miyake |
Masahiro |
M |
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| Yap |
Maurice K H |
MK |
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| Fossarello |
Maurizio |
M |
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| Kähönen |
Mika |
M |
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| Tedja |
Milly S |
MS |
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| He |
Mingguang |
M |
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| Yoshimura |
Nagahisa |
N |
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| Martin |
Nicholas G |
NG |
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| Timpson |
Nicholas J |
NJ |
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| Wareham |
Nick J |
NJ |
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| Mizuki |
Nobuhisa |
N |
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| Pfeiffer |
Norbert |
N |
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| Pärssinen |
Olavi |
O |
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| Raitakari |
Olli |
O |
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| Polasek |
Ozren |
O |
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| Tam |
Pancy O |
PO |
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| Foster |
Paul J |
PJ |
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| Mitchell |
Paul |
P |
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| Baird |
Paul Nigel |
PN |
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| Chen |
Peng |
P |
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| Hysi |
Pirro G |
PG |
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| Cumberland |
Phillippa |
P |
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| Gharahkhani |
Puya |
P |
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| Fan |
Qiao |
Q |
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| Höhn |
René |
R |
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| Fogarty |
Rhys D |
RD |
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| Luben |
Robert N |
RN |
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| Igo Jr |
Robert P |
RP |
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| Plomin |
Robert |
R |
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| Wojciechowski |
Robert |
R |
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| Klein |
Ronald |
R |
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| Mohsen Hosseini |
S |
S |
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| Janmahasatian |
Sarayut |
S |
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| Saw |
Seang-Mei |
SM |
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| Yazar |
Seyhan |
S |
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| Ping Yip |
Shea |
S |
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| Feng |
Sheng |
S |
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| Vaccargiu |
Simona |
S |
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| Panda-Jonas |
Songhomitra |
S |
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| MacGregor |
Stuart |
S |
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| Iyengar |
Sudha K |
SK |
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| Rantanen |
Taina |
T |
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| Lehtimäki |
Terho |
T |
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| Young |
Terri L |
TL |
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| Meitinger |
Thomas |
T |
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| Wong |
Tien-Yin |
TY |
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| Aung |
Tin |
T |
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| Haller |
Toomas |
T |
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| Vitart |
Veronique |
V |
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| Nangia |
Vinay |
V |
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| Verhoeven |
Virginie J M |
VJ |
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| Jhanji |
Vishal |
V |
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| Zhao |
Wanting |
W |
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| Chen |
Wei |
W |
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| Zhou |
Xiangtian |
X |
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| Guo |
Xiaobo |
X |
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| Ding |
Xiaohu |
X |
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| Wang |
Ya Xing |
YX |
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| Lu |
Yi |
Y |
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| Teo |
Yik-Ying |
YY |
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| Vatavuk |
Zoran |
Z |
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| JOURNAL |
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| VOLUME: 6 |
| ISSUE: |
| TITLE: Scientific reports |
| ISOABBREVIATION: Sci Rep |
| YEAR: |
| MONTH: |
| DAY: |
| MEDLINEDATE: 2016 |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2045-2322 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Sci Rep |
| COUNTRY: England |
| ISSNLINKING: 2045-2322 |
| NLMUNIQUEID: 101563288 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| JOURNAL ARTICLE |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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