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

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

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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