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| PMID |
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| TITLE |
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| Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia. |
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| ABSTRACT |
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| Importance |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. |
| Objective |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. |
| Design, Setting, and Participants |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. |
| Exposures |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. |
| Main Outcomes and Measures |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. Odds ratios (ORs) of polygenic risk scores in replication samples. |
| Results |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. Odds ratios (ORs) of polygenic risk scores in replication samples. A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16). |
| Conclusions and Relevance |
NlmCategory: UNASSIGNED |
| Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. Odds ratios (ORs) of polygenic risk scores in replication samples. A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16). Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| entrez |
2021/04/08 12:38 |
| pubmed |
2021/04/09 06:00 |
| medline |
2021/04/09 06:00 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Tideman JWL |
|
Tideman |
J Willem L |
JWL |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. |
| Pärssinen O |
|
Pärssinen |
Olavi |
O |
|
Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland. |
| Haarman AEG |
|
Haarman |
Annechien E G |
AEG |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. |
| Khawaja AP |
|
Khawaja |
Anthony P |
AP |
|
NIHR Biomedical Research Centre, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom. |
| Wedenoja J |
|
Wedenoja |
Juho |
J |
|
Department of Public Health, University of Helsinki, Helsinki, Finland. |
| Williams KM |
|
Williams |
Katie M |
KM |
|
Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. |
| Biino G |
|
Biino |
Ginevra |
G |
|
Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy. |
| Ding X |
|
Ding |
Xiaohu |
X |
|
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. |
| Kähönen M |
|
Kähönen |
Mika |
M |
|
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland. |
| Lehtimäki T |
|
Lehtimäki |
Terho |
T |
|
Department of Clinical Chemistry, Finnish Cardiovascular Research Center, Tampere, Finland. |
| Raitakari OT |
|
Raitakari |
Olli T |
OT |
|
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland. |
| Cheng CY |
|
Cheng |
Ching-Yu |
CY |
|
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. |
| Jonas JB |
|
Jonas |
Jost B |
JB |
|
Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China. |
| Young TL |
|
Young |
Terri L |
TL |
|
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison. |
| Bailey-Wilson JE |
|
Bailey-Wilson |
Joan E |
JE |
|
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland. |
| Rahi J |
|
Rahi |
Jugnoo |
J |
|
UCL Great Ormond Street Institute of Child Health and Institute of Ophthalmology, University College London, London, United Kingdom. |
| Williams C |
|
Williams |
Cathy |
C |
|
Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. |
| He M |
|
He |
Mingguang |
M |
|
Centre for Eye Research Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. |
| Mackey DA |
|
Mackey |
David A |
DA |
|
Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia. |
| Guggenheim JA |
|
Guggenheim |
Jeremy A |
JA |
|
Cardiff University School of Optometry and Vision Sciences, Cardiff, United Kingdom. |
|
UK Biobank Eye and Vision Consortium and the Consortium for Refractive Error and Myopia (CREAM Consortium) |
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| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Iglesias |
Adriana I |
AI |
|
| Meguro |
Akira |
A |
|
| Tsujikawa |
Akitaka |
A |
|
| Hewitt |
Alex W |
AW |
|
| Barathi |
Veluchamy A |
VA |
|
| Metspalu |
Andres |
A |
|
| Paterson |
Andrew D |
AD |
|
| Haarman |
Annechien E G |
AEG |
|
| Musolf |
Anthony |
A |
|
| Khawaja |
Anthony P |
AP |
|
| Klein |
Barbara E |
BE |
|
| Middlebrooks |
Candace |
C |
|
| Hayward |
Caroline |
C |
|
| Williams |
Cathy |
C |
|
| Delcourt |
Cécile |
C |
|
| Pang |
Chi Pui |
CP |
|
| Cheng |
Ching-Yu |
CY |
|
| Hammond |
Christopher J |
CJ |
|
| Simpson |
Claire L |
CL |
|
| van Duijn |
Cornelia M |
CM |
|
| Mackey |
David A |
DA |
|
| Lewis |
Deyana |
D |
|
| Stambolian |
Dwight |
D |
|
| Chew |
Emily Y |
EY |
|
| Tai |
E-Shyong |
ES |
|
| Biino |
Ginevra |
G |
|
| Campbell |
Harry |
H |
|
| Rudan |
Igor |
I |
|
| Tideman |
J Willem L |
JWL |
|
| Kaprio |
Jaakko |
J |
|
| Wilson |
James F |
JF |
|
| Craig |
Jamie E |
JE |
|
| Yam |
Jason C S |
JCS |
|
| Guggenheim |
Jeremy A |
JA |
|
| Bailey-Wilson |
Joan E |
JE |
|
| Lass |
Jonathan H |
JH |
|
| Jonas |
Jost B |
JB |
|
| Rahi |
Jugnoo S |
JS |
|
| Wedenoja |
Juho |
J |
|
| Burdon |
Kathryn P |
KP |
|
| Williams |
Katie M |
KM |
|
| Yamashiro |
Kenji |
K |
|
| Oexle |
Konrad |
K |
|
| Lee |
Kris |
K |
|
| Lyytikäinen |
Leo-Pekka |
LP |
|
| Chen |
Li Jia |
LJ |
|
| Deangelis |
Margaret M |
MM |
|
| Miyake |
Masahiro |
M |
|
| Yap |
Maurice K H |
MKH |
|
| Fossarello |
Maurizio |
M |
|
| Kähönen |
Mika |
M |
|
| Tedja |
Milly S |
MS |
|
| He |
Mingguang |
M |
|
| Martin |
Nicholas G |
NG |
|
| Wang |
Ningli |
N |
|
| Mizuki |
Nobuhisa |
N |
|
| Pfeiffer |
Norbert |
N |
|
| Pärssinen |
Olavi |
O |
|
| Raitakari |
Olli |
O |
|
| Polasek |
Ozren |
O |
|
| Foster |
Paul J |
PJ |
|
| Baird |
Paul N |
PN |
|
| Hysi |
Pirro G |
PG |
|
| Gharahkhani |
Puya |
P |
|
| Fan |
Qiao |
Q |
|
| Li |
Qing |
Q |
|
| Hoang |
Quan |
Q |
|
| Igo |
Robert P |
RP |
|
| Wojciechowski |
Robert |
R |
|
| Saw |
Seang-Mei |
SM |
|
| Yazar |
Seyhan |
S |
|
| Yip |
Shea Ping |
SP |
|
| Li |
Shi-Ming |
SM |
|
| Sahebjada |
Srujana |
S |
|
| Nickels |
Stefan |
S |
|
| MacGregor |
Stuart |
S |
|
| Iyengar |
Sudha K |
SK |
|
| Lehtimäki |
Terho |
T |
|
| Young |
Terri L |
TL |
|
| Haller |
Toomas |
T |
|
| Vitart |
Veronique |
V |
|
| Verhoeven |
Virginie J M |
VJM |
|
| Wei |
Wen Bin |
WB |
|
| Zhou |
Xiangtian |
X |
|
| Guo |
Xiaobo |
X |
|
| Ding |
Xiaohu |
X |
|
| Han |
Xikun |
X |
|
| Wang |
Ya Xing |
YX |
|
| Allen |
Naomi |
N |
|
| Aslam |
Tariq |
T |
|
| Atan |
Denize |
D |
|
| Barman |
Sarah |
S |
|
| Barrett |
Jenny |
J |
|
| Bishop |
Paul |
P |
|
| Black |
Graeme |
G |
|
| Bunce |
Catey |
C |
|
| Carare |
Roxana |
R |
|
| Chakravarthy |
Usha |
U |
|
| Chan |
Michelle |
M |
|
| Chua |
Sharon |
S |
|
| Cipriani |
Valentina |
V |
|
| Day |
Alexander |
A |
|
| Desai |
Parul |
P |
|
| Dhillon |
Bal |
B |
|
| Dick |
Andrew |
A |
|
| Doney |
Alexander |
A |
|
| Egan |
Cathy |
C |
|
| Ennis |
Sarah |
S |
|
| Foster |
Paul |
P |
|
| Fruttiger |
Marcus |
M |
|
| Gallacher |
John |
J |
|
| Garway-Heath |
David |
D |
|
| Gibson |
Jane |
J |
|
| Gore |
Dan |
D |
|
| Guggenheim |
Jeremy |
J |
|
| Hammond |
Chris |
C |
|
| Hardcastle |
Alison |
A |
|
| Harding |
Simon |
S |
|
| Hogg |
Ruth |
R |
|
| Hysi |
Pirro |
P |
|
| Keane |
Pearse A |
PA |
|
| Khaw |
Peng Tee |
PT |
|
| Khawaja |
Anthony |
A |
|
| Lascaratos |
Gerassimos |
G |
|
| Littlejohns |
Thomas |
T |
|
| Lotery |
Andrew |
A |
|
| Luthert |
Phil |
P |
|
| Macgillivray |
Tom |
T |
|
| Mackie |
Sarah |
S |
|
| Mcguinness |
Bernadette |
B |
|
| Mckay |
Gareth |
G |
|
| Mckibbin |
Martin |
M |
|
| Mitry |
Danny |
D |
|
| Moore |
Tony |
T |
|
| Morgan |
James |
J |
|
| Muthy |
Zaynah |
Z |
|
| O'sullivan |
Eoin |
E |
|
| Owen |
Chris |
C |
|
| Patel |
Praveen |
P |
|
| Paterson |
Euan |
E |
|
| Peto |
Tunde |
T |
|
| Petzold |
Axel |
A |
|
| Pontikos |
Nikolas |
N |
|
| Rahi |
Jugnoo |
J |
|
| Rudnicka |
Alicja |
A |
|
| Self |
Jay |
J |
|
| Sergouniotis |
Panagiotis |
P |
|
| Sivaprasad |
Sobha |
S |
|
| Steel |
David |
D |
|
| Stratton |
Irene |
I |
|
| Strouthidis |
Nicholas |
N |
|
| Sudlow |
Cathie |
C |
|
| Tapp |
Robyn |
R |
|
| Thaung |
Caroline |
C |
|
| Thomas |
Dhanes |
D |
|
| Trucco |
Emanuele |
E |
|
| Tufail |
Adnan |
A |
|
| Vernon |
Stephen |
S |
|
| Viswanathan |
Ananth |
A |
|
| Williams |
Katie |
K |
|
| Woodside |
Jayne |
J |
|
| Yates |
Max |
M |
|
| Yip |
Jennifer |
J |
|
| Zheng |
Yalin |
Y |
|
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: JAMA ophthalmology |
| ISOABBREVIATION: JAMA Ophthalmol |
| YEAR: 2021 |
| MONTH: Apr |
| DAY: 08 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2168-6173 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: JAMA Ophthalmol |
| COUNTRY: United States |
| ISSNLINKING: 2168-6165 |
| NLMUNIQUEID: 101589539 |
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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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