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

Published version
Peer-reviewed

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Authors

Bonnemaijer, Pieter WM  ORCID logo  https://orcid.org/0000-0001-5154-6765
Leeuwen, Elisabeth M van 
Iglesias, Adriana I  ORCID logo  https://orcid.org/0000-0001-5532-764X

Abstract

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.

Description

Funder: All funders per study are acknowledged in the Supplementary File

Keywords

Genome-wide association studies, Optic nerve diseases, Case-Control Studies, Computational Biology, Gene Expression Profiling, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Humans, Molecular Sequence Annotation, Optic Disk, Optic Nerve Diseases, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Signal Transduction

Journal Title

Commun Biol

Conference Name

Journal ISSN

2399-3642
2399-3642

Volume Title

2

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)