TY - JOUR
T1 - Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
AU - Gharahkhani, Puya
AU - Jorgenson, Eric
AU - Hysi, Pirro
AU - Khawaja, Anthony P
AU - Pendergrass, Sarah
AU - Han, Xikun
AU - Ong, Jue Sheng
AU - Hewitt, Alex W
AU - Segrè, Ayellet V
AU - Rouhana, John M
AU - Hamel, Andrew R
AU - Igo, Robert P
AU - Choquet, Helene
AU - Qassim, Ayub
AU - Josyula, Navya S
AU - Cooke Bailey, Jessica N
AU - Bonnemaijer, Pieter W M
AU - Iglesias, Adriana
AU - Siggs, Owen M
AU - Young, Terri L
AU - Vitart, Veronique
AU - Thiadens, Alberta A H J
AU - Karjalainen, Juha
AU - Uebe, Steffen
AU - Melles, Ronald B
AU - Nair, K Saidas
AU - Luben, Robert
AU - Simcoe, Mark
AU - Amersinghe, Nishani
AU - Cree, Angela J
AU - Hohn, Rene
AU - Poplawski, Alicia
AU - Chen, Li Jia
AU - Rong, Shi-Song
AU - Aung, Tin
AU - Vithana, Eranga Nishanthie
AU - Tamiya, Gen
AU - Shiga, Yukihiro
AU - Yamamoto, Masayuki
AU - Nakazawa, Toru
AU - Currant, Hannah
AU - Birney, Ewan
AU - Wang, Xin
AU - Auton, Adam
AU - Lupton, Michelle K
AU - Martin, Nicholas G
AU - Ashaye, Adeyinka
AU - Olawoye, Olusola
AU - Williams, Susan E
AU - Akafo, Stephen
AU - NEIGHBORHOOD consortium
PY - 2021/2/24
Y1 - 2021/2/24
N2 - Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
AB - Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
KW - Asian Continental Ancestry Group
KW - European Continental Ancestry Group
KW - Genetic Loci/genetics
KW - Genetic Predisposition to Disease/genetics
KW - Genome-Wide Association Study/methods
KW - Genotype
KW - Glaucoma, Open-Angle/genetics
KW - Humans
KW - Polymorphism, Single Nucleotide/genetics
U2 - 10.1038/s41467-020-20851-4
DO - 10.1038/s41467-020-20851-4
M3 - Article
C2 - 33627673
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1258
ER -