TY - JOUR
T1 - Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
AU - Bonnemaijer, Pieter W.M.
AU - van Leeuwen, Elisabeth M.
AU - Iglesias, Adriana I.
AU - Gharahkhani, Puya
AU - Vitart, Veronique
AU - Khawaja, Anthony P.
AU - Simcoe, Mark
AU - Höhn, René
AU - Cree, Angela J.
AU - Igo, Rob P.
AU - International Glaucoma Genetics Consortium
AU - Burdon, Kathryn P.
AU - Craig, Jamie E.
AU - Hewitt, Alex W.
AU - Jonas, Jost
AU - Khor, Chiea Cheun
AU - Pasutto, Francesca
AU - Mackey, David A.
AU - Mitchell, Paul
AU - Mishra, Aniket
AU - Pang, Calvin
AU - Pasquale, Louis R.
AU - Springelkamp, Henriette
AU - Thorleifsson, Gudmar
AU - Thorsteinsdottir, Unnur
AU - Viswanathan, Ananth C.
AU - Wojciechowski, Robert
AU - Wong, Tien
AU - Young, Terrri L.
AU - Zeller, Tanja
AU - NEIGHBORHOOD Consortium
AU - Allingham, Rand
AU - Budenz, Don
AU - Bailey, Jessica Cooke
AU - Fingert, John
AU - Gaasterland, Douglas
AU - Gaasterland, Teresa
AU - Haines, Jonathan L.
AU - Hark, Lisa
AU - Hauser, Michael
AU - Kang, Jae Hee
AU - Kraft, Peter
AU - Lee, Richard
AU - Lichter, Paul
AU - Liu, Yutao
AU - Moroi, Syoko
AU - Pasquale, Louis R.
AU - Pericak, Margaret
AU - Realini, Anthony
AU - Rhee, Doug
AU - Richards, Julia R.
AU - Ritch, Robert
AU - Scott, William K.
AU - Singh, Kuldev
AU - Sit, Arthur
AU - Vollrath, Douglas
AU - Weinreb, Robert
AU - Wollstein, Gadi
AU - Wilmer, Don Zack
AU - UK Biobank Eye and Vision Consortium
AU - Atan, Denize
AU - Aslam, Tariq
AU - Barman, Sarah A.
AU - Barrett, Jenny H.
AU - Bishop, Paul
AU - Blows, Peter
AU - Bunce, Catey
AU - Carare, Roxana O.
AU - Chakravarthy, Usha
AU - Chan, Michelle
AU - Chua, Sharon Y.L.
AU - Crabb, David P.
AU - Cumberland, Philippa M.
AU - Day, Alexander
AU - Desai, Parul
AU - Dhillon, Bal
AU - Dick, Andrew D.
AU - Egan, Cathy
AU - Ennis, Sarah
AU - Foster, Paul
AU - Fruttiger, Marcus
AU - Gallacher, John E.J.
AU - Garway, David F.
AU - Gibson, Jane
AU - Gore, Dan
AU - Guggenheim, Jeremy A.
AU - Hardcastle, Alison
AU - Harding, Simon P.
AU - Hogg, Ruth E.
AU - Keane, Pearse A.
AU - Khaw, Peng T.
AU - Lascaratos, Gerassimos
AU - Macgillivray, Tom
AU - Mackie, Sarah
AU - Martin, Keith
AU - McGaughey, Michelle
AU - McGuinness, Bernadette
AU - McKay, Gareth J.
AU - McKibbin, Martin
AU - Mitry, Danny
AU - Moore, Tony
AU - Morgan, James E.
AU - Muthy, Zaynah A.
AU - O’Sullivan, Eoin
AU - Owen, Chris G.
AU - Patel, Praveen
AU - Paterson, Euan
AU - Peto, Tunde
AU - Petzold, Axel
AU - Rahi, Jugnoo S.
AU - Rudnikca, Alicja R.
AU - Self, Jay
AU - Sivaprasad, Sobha
AU - Steel, David
AU - Stratton, Irene
AU - Strouthidis, Nicholas
AU - Sudlow, Cathie
AU - Thomas, Dhanes
AU - Trucco, Emanuele
AU - Tufail, Adnan
AU - Vernon, Stephen A.
AU - Viswanathan, Ananth C.
AU - Williams, Cathy
AU - Williams, Katie
AU - Woodside, Jayne V.
AU - Yates, Max M.
AU - Yip, Jennifer
AU - Zheng, Yalin
AU - Gerhold-Ay, Aslihan
AU - Nickels, Stefan
AU - Wilson, James F.
AU - Hayward, Caroline
AU - Boutin, Thibaud S.
AU - Polašek, Ozren
AU - Aung, Tin
AU - Khor, Chiea Chuen
AU - Amin, Najaf
AU - Lotery, Andrew J.
AU - Wiggs, Janey L.
AU - Cheng, Ching Yu
AU - Hysi, Pirro G.
AU - Hammond, Christopher J.
AU - Thiadens, Alberta A.H.J.
AU - MacGregor, Stuart
AU - Klaver, Caroline C.W.
AU - Duijn, Cornelia M.van
N1 - Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - genome-wide
KW - optic disc parameters
KW - Multi-trait
KW - identifies new loci
UR - http://www.scopus.com/inward/record.url?scp=85075712104&partnerID=8YFLogxK
U2 - 10.1038/s42003-019-0634-9
DO - 10.1038/s42003-019-0634-9
M3 - Article
C2 - 31925227
AN - SCOPUS:85075712104
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 435
ER -