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, 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, Gore D, 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, 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, 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

Journal

Book Volume: 2

Article Number: 435

Journal Issue: 1

DOI: 10.1038/s42003-019-0634-9

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.

Authors with CRIS profile

Involved external institutions

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

How to cite

APA:

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

MLA:

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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