Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
Authors: Bonnemaijer Pieter W. M. , Leeuwen Elisabeth M. van , Iglesias Adriana I. , Gharahkhani Puya , Vitart Veronique , Khawaja Anthony P. , Simcoe Mark , Höhn René , Cree Angela J. , Igo Rob P. ,   International Glaucoma Genetics Consortium, Burdon Kathryn P. , Craig Jamie E. , Hewitt Alex W. , Jonas Jost , Khor Chiea-Cheun , Pasutto Francesca , Mackey David A. , Mitchell Paul , Mishra Aniket , Pang Calvin , Pasquale Louis R , Springelkamp Henriette , Thorleifsson Gudmar , Thorsteinsdottir Unnur , Viswanathan Ananth C. , Wojciechowski Robert , Wong Tien , Young Terrri L , Zeller Tanja ,   NEIGHBORHOOD consortium, Allingham Rand , Budenz Don , Bailey Jessica Cooke , Fingert John , Gaasterland Douglas , Gaasterland Teresa , Haines Jonathan L. , Hark Lisa , Hauser Michael , Kang Jae Hee , Kraft Peter , Lee Richard , Lichter Paul , Liu Yutao , Moroi Syoko , Pasquale Louis R. , Pericak Margaret , Realini Anthony , Rhee Doug , Richards Julia R. , Ritch Robert , Scott William K. , Singh Kuldev , Sit Arthur , Vollrath Douglas , Weinreb Robert , Wollstein Gadi , Wilmer Don Zack ,   UK Biobank Eye and Vision Consortium, Atan Denize , Aslam Tariq , Barman Sarah A. , Barrett Jenny H. , Bishop Paul , Blows Peter , Bunce Catey , Carare Roxana O. , Chakravarthy Usha , Chan Michelle , Chua Sharon Y. L. , Crabb David P. , Cumberland Philippa M. , Day Alexander , Desai Parul , Dhillon Bal , Dick Andrew D. , Egan Cathy , Ennis Sarah , Foster Paul , Fruttiger Marcus , Gallacher John E. J. , Garway David F. , Gibson Jane , Dan Gore  , Guggenheim Jeremy A. , Hardcastle Alison , Harding Simon P. , Hogg Ruth E. , Keane Pearse A. , Khaw Peng T. , Lascaratos Gerassimos , Macgillivray Tom , Mackie Sarah , Martin Keith , McGaughey Michelle , McGuinness Bernadette , McKay Gareth J. , McKibbin Martin , Mitry Danny , Moore Tony , Morgan James E. , Muthy Zaynah A. , O’Sullivan Eoin , Owen Chris G. , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Rahi Jugnoo S. , Rudnikca Alicja R. , Self Jay , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Thomas Dhanes , Trucco Emanuele , Tufail Adnan , Vernon Stephen A. , Viswanathan Ananth C. , Williams Cathy , Williams Katie , Woodside Jayne V. , Yates Max M. , Yip Jennifer , Zheng Yalin , Gerhold-Ay Aslihan , Nickels Stefan , Wilson James F. , Hayward Caroline , Boutin Thibaud S. , Polašek Ozren , Aung Tin , Khor Chiea Chuen , Amin Najaf , Lotery Andrew J. , Wiggs Janey L. , Cheng Ching-Yu , Hysi Pirro G. , Hammond Christopher J. , Thiadens Alberta A. H. J. , MacGregor Stuart , Klaver Caroline C. W. , Duijn Cornelia M. van 
Published: November 2019

AbstractA 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.