TY - JOUR
T1 - Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images
AU - Currant, Hannah
AU - Hysi, Pirro
AU - Fitzgerald, Tomas W.
AU - Gharahkhani, Puya
AU - Bonnemaijer, Pieter W.M.
AU - Senabouth, Anne
AU - Hewitt, Alex W.
AU - UK Biobank Eye and Vision Consortium
AU - International Glaucoma Genetics Consortium
AU - Atan, Denize
AU - Aung, Tin
AU - Charng, Jason
AU - Choquet, Hélène
AU - Craig, Jamie
AU - Khaw, Peng T.
AU - Klaver, Caroline C.W.
AU - Kubo, Michiaki
AU - Ong, Jue Sheng
AU - Pasquale, Louis R.
AU - Reisman, Charles A.
AU - Daniszewski, Maciej
AU - Powell, Joseph E.
AU - Pébay, Alice
AU - Simcoe, Mark J.
AU - Thiadens, Alberta A.H.J.
AU - van Duijn, Cornelia M.
AU - Yazar, Seyhan
AU - Jorgenson, Eric
AU - MacGregor, Stuart
AU - Hammond, Chris J.
AU - Mackey, David A.
AU - Wiggs, Janey L.
AU - Foster, Paul J.
AU - Patel, Praveen J.
AU - Birney, Ewan
AU - Khawaja, Anthony P.
N1 - A correction to this publication was published 18 October 2021.
PY - 2021/5/12
Y1 - 2021/5/12
N2 - Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
AB - Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
KW - Biomarkers
KW - Glaucoma
KW - retinal morphology
KW - phenotypes
UR - http://www.scopus.com/inward/record.url?scp=85106246074&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1173390
UR - http://purl.org/au-research/grants/NHMRC/1154543
UR - http://purl.org/au-research/grants/NHMRC/1150144
UR - http://purl.org/au-research/grants/NHMRC/1116360
U2 - 10.1371/journal.pgen.1009497
DO - 10.1371/journal.pgen.1009497
M3 - Article
C2 - 33979322
AN - SCOPUS:85106246074
VL - 17
JO - PloS Genetics
JF - PloS Genetics
SN - 1553-7390
IS - 5
M1 - e1009497
ER -