Pieter W. M. Bonnemaijer, Erasmus MC, The Rotterdam Eye Hospital
Elisabeth M. van Leeuwen, Erasmus MC
Adriana I. Iglesias, Erasmus MC
Puya Gharahkhani, MR Berghofer Medical Research Institute, Royal Brisbane Hospital
Veronique Vitart, Institute of Genetics and Molecular Medicine, University of Edinburgh
Anthony P. Khawaja, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology
Mark Simcoe, Twin Research and Genetic Epidemiology, King’s College London
René Höhn, University of Bern, University Medical Center Mainz
Angela J. Cree, University of Southampton
Rob P. Igo, Harvard Medical School
International Glaucoma Genetics Consortium
UK Biobank Eye and Vision Consortium
Aslihan Gerhold-Ay, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz
Stefan Nickels, Department of Ophthalmology, University Medical Center Mainz
James F. Wilson, University of Edinburgh
Caroline Hayward, University of Edinburgh
Thibaud S. Boutin, University of Edinburgh
Ozren Polašek, Faculty of Medicine, University of Split
Tin Aung, Singapore Eye Research Institute, Singapore National Eye Centre,
Chiea Chuen Khor, Division of Human Genetics, Genome Institute of Singapore
Najaf Amin, Erasmus MC
Andrew J. Lotery, Faculty of Medicine, University of Southampton
Janey L. Wiggs, Harvard Medical School
Ching-Yu Cheng, Singapore Eye Research Institute, Singapore National Eye Centre
Pirro G. Hysi, Twin Research and Genetic Epidemiology, King’s College London
Christopher J. Hammond, Twin Research and Genetic Epidemiology, King’s College London
Alberta A. H. J. Thiadens, Erasmus MC
Stuart MacGregor, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital
Caroline C. W. Klaver, Erasmus MC, Radboud Medical Center, Institute for Molecular and Clinical Ophthalmology
Cornelia M. van Duijn, Erasmus MC, University of Oxford

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A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Source Citation

Bonnemaijer, P. W. M., Leeuwen, E. M. van, Iglesias, A. I., Gharahkhani, P., Vitart, V., Khawaja, A. P., Simcoe, M., Höhn, R., Cree, A. J., Igo, R. P., Gerhold-Ay, A., Nickels, S., Wilson, J. F., Hayward, C., Boutin, T. S., Polašek, O., Aung, T., … Khor, C. C. (2019). Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Communications Biology, 2(1).


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