TY - JOUR
T1 - Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
AU - Bonnemaijer, Pieter W.M.
AU - Leeuwen, Elisabeth M.van
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 - 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 - 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 - Scott, William K.
AU - Blows, Peter
AU - Chakravarthy, Usha
AU - Foster, Paul
AU - Hogg, Ruth E.
AU - McGaughey, Michelle
AU - McGuinness, Bernadette
AU - McKay, Gareth J.
AU - Paterson, Euan
AU - Peto, Tunde
AU - Steel, David
AU - Woodside, Jayne V.
AU - International Glaucoma Genetics Consortium
AU - NEIGHBORHOOD consortium
AU - UK Biobank Eye and Vision Consortium
N1 - Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/11/27
Y1 - 2019/11/27
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.
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 -