TY - JOUR
T1 - Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
AU - Bonnemijer, Pieter
AU - van Leeuwen, E
AU - Iglesias, Adriana I.
AU - Gharahkhani, Puya
AU - Vitart, Veronique
AU - Khawaja, Anthony P.
AU - Simcoe, Mark
AU - Hohn, René
AU - Cree, Angela
AU - Igo, Robert P.
AU - International Glaucoma Genetics Consortium
AU - NEIGHBORHOOD consortium
AU - UK Biobank Eye and Vision Consortium
AU - Atan, Denize
AU - van Duijn, Cornelia
AU - et, al
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.
KW - Genome-wide association studies
KW - Optic nerve diseases
U2 - 10.1038/s42003-019-0634-9
DO - 10.1038/s42003-019-0634-9
M3 - Article (Academic Journal)
C2 - 31798171
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
M1 - 435 (2019)
ER -