Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Pieter W M Bonnemaijer; Elisabeth M van Leeuwen; Adriana I Iglesias; Puya Gharahkhani; Veronique Vitart; Anthony P Khawaja; Mark Simcoe; René Höhn; Angela J Cree; Rob P Igo; Aslihan Gerhold-Ay; Stefan Nickels; James F Wilson; Caroline Hayward; Thibaud S Boutin; Ozren Polašek; Tin Aung; Chiea Chuen Khor; Najaf Amin; Andrew J Lotery; Janey L Wiggs; Ching-Yu Cheng; Pirro G Hysi; Christopher J Hammond; Alberta A H J Thiadens; Stuart MacGregor; Caroline C W Klaver; Cornelia M van Duijn; International Glaucoma Genetics Consortium

doi:10.1038/s42003-019-0634-9

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Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Journal article

Open access

Peer reviewed

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Pieter W M Bonnemaijer, Elisabeth M van Leeuwen, Adriana I Iglesias, Puya Gharahkhani, Veronique Vitart, Anthony P Khawaja, Mark Simcoe, René Höhn, Angela J Cree, Rob P Igo, …

Communications biology, Vol.2(1), pp.435-435

2019

DOI: https://doi.org/10.1038/s42003-019-0634-9

PMID: 31798171

Abstract

Case-Control Studies

Computational Biology

Gene Expression Profiling

Genetic Association Studies

Genetic Predisposition to Disease

Genome-Wide Association Study

Glaucoma - diagnosis

Glaucoma - genetics

Humans

Molecular Sequence Annotation

Optic Disk - metabolism

Optic Nerve Diseases - genetics

Optic Nerve Diseases - pathology

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Quantitative Trait, Heritable

Signal Transduction

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 and rs1028727 near 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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.36 Ophthalmology; 1.36.226 Glaucoma
Web Of Science research areas: Biology
ESI research areas: Biology & Biochemistry

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Title: Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
Creators: Pieter W M Bonnemaijer - 3The Rotterdam Eye Hospital, Rotterdam, The Netherlands
Elisabeth M van Leeuwen - 2Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Adriana I Iglesias - 4Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Puya Gharahkhani - Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia
Veronique Vitart - 6Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Anthony P Khawaja - 7NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
Mark Simcoe - 8Twin Research and Genetic Epidemiology, King's College London, London, UK
René Höhn - 10Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany
Angela J Cree - 11Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
Rob P Igo - 12Department of Ophthalmology, Harvard Medical School, Boston, MA USA
Aslihan Gerhold-Ay - 13Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany
Stefan Nickels - 10Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany
James F Wilson - 14Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
Caroline Hayward - 6Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Thibaud S Boutin - 6Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Ozren Polašek - 15Faculty of Medicine, University of Split, Split, Croatia
Tin Aung - 18Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Chiea Chuen Khor - 19Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore
Najaf Amin - 2Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Andrew J Lotery - 11Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
Janey L Wiggs - 12Department of Ophthalmology, Harvard Medical School, Boston, MA USA
Ching-Yu Cheng - 18Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Pirro G Hysi - 8Twin Research and Genetic Epidemiology, King's College London, London, UK
Christopher J Hammond - 8Twin Research and Genetic Epidemiology, King's College London, London, UK
Alberta A H J Thiadens - 2Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Stuart MacGregor - Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia
Caroline C W Klaver - Institute for Molecular and Clinical Ophthalmology, Basel, Switzerland
Cornelia M van Duijn - 22Nuffield Department of Public Health, University of Oxford, Oxford, UK
International Glaucoma Genetics Consortium
Publication Details: Communications biology, Vol.2(1), pp.435-435
Grant note: R01 EY015872 / NEI NIH HHS G0401527 / Medical Research Council CZB/4/276 / Chief Scientist Office Wellcome Trust MC_UU_00007/10 / Medical Research Council MR/N003284/1 / Medical Research Council R01 EY019126 / NEI NIH HHS C864/A14136 / Cancer Research UK R01 EY023242 / NEI NIH HHS R01 EY022305 / NEI NIH HHS HHSN268200782096C / NHGRI NIH HHS R01 EY024233 / NEI NIH HHS CS-2014-14-023 / Department of Health 14136 / Cancer Research UK R21 EY028671 / NEI NIH HHS CZB/4/710 / Chief Scientist Office Arthritis Research UK MC_PC_13048 / Medical Research Council G1000143 / Medical Research Council
Language: English
Resource Type: Journal article
PMID: 31798171
Record Identifier: 991031614705302976