Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.,Nature Genetics

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Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.
Nature Genetics ( IF 31.7 ) Pub Date : 2020-03-30 , DOI: 10.1038/s41588-020-0599-0
Pirro G Hysi _{1,

2,

3} , Hélène Choquet ₄ , Anthony P Khawaja _{5,

6} , Robert Wojciechowski _{7,

8} , Milly S Tedja _{9,

10} , Jie Yin ₄ , Mark J Simcoe ₂ , Karina Patasova ₁ , Omar A Mahroo _{1,

5} , Khanh K Thai ₄ , Phillippa M Cumberland _{3,

11} , Ronald B Melles ₁₂ , Virginie J M Verhoeven _{9,

10,

13} , Veronique Vitart ₁₄ , Ayellet Segre ₁₅ , Richard A Stone ₁₆ , Nick Wareham ₆ , Alex W Hewitt ₁₇ , David A Mackey _{17,

18} , Caroline C W Klaver _{9,

10,

19,

20} , Stuart MacGregor ₂₁ , , Peng T Khaw ₅ , Paul J Foster _{5,

22} , , Jeremy A Guggenheim ₂₃ , , Jugnoo S Rahi _{3,

5,

11,

24} , Eric Jorgenson ₄ , Christopher J Hammond _{1,

2}

Affiliation

Section of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.
Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Ulverscroft Vision Research Group, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Department of Ophthalmology Kaiser Permanente Northern California, Redwood City, CA, USA.
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA, USA.
Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Ophthalmology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Western Australia, Australia.
Department of Ophthalmology, Radboud University Medical Center, Rotterdam, the Netherlands.
Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK.
School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK.
Department of Ophthalmology and NIHR, Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.

中文翻译：

对 542,934 名欧洲血统受试者的荟萃分析确定了易患屈光不正和近视的新基因和机制。

屈光不正，尤其是近视，是全世界发病率和残疾的主要原因。基因研究可以提高对导致眼睛发育异常和视力受损的分子机制的理解。我们对涉及 542,934 名欧洲参与者的全基因组关联研究 (GWAS) 进行了荟萃分析，并确定了 336 个与屈光不正相关的新基因位点。总的来说，所有相关的遗传变异解释了 18.4% 的遗传力并提高了近视预测的准确性（曲线下面积 (AUC) = 0.75）。我们的研究结果表明，屈光不正具有遗传异质性，由参与眼睛每个解剖组成部分发育的基因驱动。此外，我们的分析表明，控制昼夜节律和色素沉着的遗传因素也与近视和屈光不正的发展有关。这些结果可能有助于预测屈光不正和未来制定个性化的近视预防策略。

更新日期：2020-04-24

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