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, International Glaucoma Genetics Consortium, Kathryn P. Burdon, Jamie E. Craig, Alex W. Hewitt, David A. Mackey, NEIGHBORHOOD Consortium, Jessica Cooke Bailey, UK Biobank Eye and Vision Consortium, Jenny H. Barrett, Paul FosterTony Moore, 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, Ching Yu Cheng, Pirro G. Hysi, Christopher J. Hammond, Alberta A.H.J. Thiadens, Stuart MacGregor, Caroline C.W. Klaver, Cornelia M.van Duijn

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Article number435
JournalCommunications Biology
Issue number1
Publication statusPublished - 1 Dec 2019

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  • genome-wide
  • optic disc parameters
  • Multi-trait
  • identifies new loci

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