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

Bonnemaijer PW, Leeuwen EM, Iglesias AI, Gharahkhani P, Vitart V, Khawaja AP, Simcoe M, Höhn R, Cree AJ, Igo RP, Burdon KP, Craig JE, Hewitt AW, Jonas J, Khor CC, Pasutto F, Mackey DA, Mitchell P, Mishra A, Pang C, Pasquale LR, Springelkamp H, Thorleifsson G, Thorsteinsdottir U, Viswanathan AC, Wojciechowski R, Wong T, Young TL, Zeller T, Allingham R, Budenz D, Bailey JC, Fingert J, Gaasterland D, Gaasterland T, Haines JL, Hark L, Hauser M, Kang JH, Kraft P, Lee R, Lichter P, Liu Y, Moroi S, Pasquale LR, Pericak M, Realini A, Rhee D, Richards JR, Ritch R, Scott WK, Singh K, Sit A, Vollrath D, Weinreb R, Wollstein G, Wilmer DZ, Atan D, Aslam T, Barman SA, Barrett JH, Bishop P, Blows P, Bunce C, Carare RO, Chakravarthy U, Chan M, Chua SY, Crabb DP, Cumberland PM, Day A, Desai P, Dhillon B, Dick AD, Egan C, Ennis S, Foster P, Fruttiger M, Gallacher JE, Garway DF, Gibson J, Dan Gore , Guggenheim JA, Hardcastle A, Harding SP, Hogg RE, Keane PA, Khaw PT, Lascaratos G, Macgillivray T, Mackie S, Martin K, McGaughey M, McGuinness B, McKay GJ, McKibbin M, Mitry D, Moore T, Morgan JE, Muthy ZA, O’Sullivan E, Owen CG, Patel P, Paterson E, Peto T, Petzold A, Rahi JS, Rudnikca AR, Self J, Sivaprasad S, Steel D, Stratton I, Strouthidis N, Sudlow C, Thomas D, Trucco E, Tufail A, Vernon SA, Viswanathan AC, Williams C, Williams K, Woodside JV, Yates MM, Yip J, Zheng Y, Gerhold-Ay A, Nickels S, Wilson JF, Hayward C, Boutin TS, Polašek O, Aung T, Khor CC, Amin N, Lotery AJ, Wiggs JL, Cheng CY, Hysi PG, Hammond CJ, Thiadens AA, MacGregor S, Klaver CC, Duijn CM (2019)

Publication Type: Journal article

Publication year: 2019


Book Volume: 2

Article Number: 435

Journal Issue: 1

DOI: 10.1038/s42003-019-0634-9


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.

Additional Organisation(s)

Involved external institutions

Inselspital, Universitätsspital Bern CH Switzerland (CH) Icahn School of Medicine at Mount Sinai US United States (USA) (US) University of Tasmania (UTAS) AU Australia (AU) Moorfields Eye Hospital NHS Foundation Trust GB United Kingdom (GB) Brigham and Women's Hospital (BWH) US United States (USA) (US) Erasmus University Medical Center (MC) NL Netherlands (NL) University of Iowa US United States (USA) (US) Johns Hopkins University (JHU) US United States (USA) (US) deCODE genetics IS Iceland (IS) Duke University Medical Center US United States (USA) (US) University of Wisconsin - Madison US United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) University of California, San Diego US United States (USA) (US) Flinders University AU Australia (AU) Thomas Jefferson University Hospitals US United States (USA) (US) MRC Institute of Genetics & Molecular Medicine MRC Human Genetics Unit GB United Kingdom (GB) University of Michigan US United States (USA) (US) Case Western Reserve University US United States (USA) (US) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) University of Western Australia (UWA) AU Australia (AU) Harvard T.H. Chan School of Public Health US United States (USA) (US) University of East Anglia GB United Kingdom (GB) King’s College London GB United Kingdom (GB) Royal Brisbane and Women's Hospital AU Australia (AU) University College London (UCL) GB United Kingdom (GB) Queen's University GB United Kingdom (GB) Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) National University of Singapore (NUS) SG Singapore (SG) New York University (NYU) US United States (USA) (US) NIHR Barts Biomedical Research Centre GB United Kingdom (GB) University of Miami US United States (USA) (US) University of Manchester GB United Kingdom (GB) University of Bristol GB United Kingdom (GB) Genome Institute of Singapore SG Singapore (SG) West Virginia University (WVU) US United States (USA) (US) Stanford University US United States (USA) (US) Leeds Teaching Hospitals NHS Trust GB United Kingdom (GB) University of Edinburgh GB United Kingdom (GB) Cardiff University GB United Kingdom (GB) University of Leeds GB United Kingdom (GB) University of Southampton GB United Kingdom (GB) University of Split / Sveučilište u Splitu HR Croatia (HR) Nottingham University Hospitals GB United Kingdom (GB) University of London GB United Kingdom (GB) The University of Liverpool GB United Kingdom (GB) Gloucestershire Hospitals GB United Kingdom (GB) University of Oxford GB United Kingdom (GB) Newcastle University GB United Kingdom (GB) University of Dundee GB United Kingdom (GB) University of Sydney (USYD) AU Australia (AU) University of Cambridge GB United Kingdom (GB) Mayo Clinic US United States (USA) (US) The Chinese University of Hong Kong (CUHK) CN China (CN) New York Eye and Ear Infirmary of Mount Sinai US United States (USA) (US) University of North Carolina at Chapel Hill US United States (USA) (US) Kingston University GB United Kingdom (GB) Augusta University US United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) The University of Melbourne AU Australia (AU)

How to cite


Bonnemaijer, P.W., Leeuwen, E.M., Iglesias, A.I., Gharahkhani, P., Vitart, V., Khawaja, A.P.,... Duijn, C.M. (2019). Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Communications Biology, 2(1).


Bonnemaijer, Pieter W.M., et al. "Multi-trait genome-wide association study identifies new loci associated with optic disc parameters." Communications Biology 2.1 (2019).

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