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
33830181
TITLE
Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia.
ABSTRACT
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.
DATE PUBLISHED
2021 Apr 08
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2021/04/08 12:38
pubmed 2021/04/09 06:00
medline 2021/04/09 06:00
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)
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
JOURNAL
VOLUME:
ISSUE:
TITLE: JAMA ophthalmology
ISOABBREVIATION: JAMA Ophthalmol
YEAR: 2021
MONTH: Apr
DAY: 08
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2168-6173
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA Ophthalmol
COUNTRY: United States
ISSNLINKING: 2168-6165
NLMUNIQUEID: 101589539
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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