A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.
Document Type
Article
Publication Date
6-11-2018
JAX Source
Nat Commun 2018 Jun 11; 9(1):2278
Volume
9
Issue
1
First Page
2278
Last Page
2278
ISSN
2041-1723
PMID
29891935
DOI
https://doi.org/10.1038/s41467-018-04555-4
Grant
EY011721
Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss, yet much of the genetic risk remains unaccounted for, especially in African-Americans who have a higher risk for developing POAG. We conduct a multiethnic genome-wide association study (GWAS) of POAG in the GERA cohort, with replication in the UK Biobank (UKB), and vice versa, GWAS in UKB with replication in GERA. We identify 24 loci (P < 5.0 × 10-8), including 14 novel, of which 9 replicate (near FMNL2, PDE7B, TMTC2, IKZF2, CADM2, DGKG, ANKH, EXOC2, and LMX1B). Functional studies support intraocular pressure-related influences of FMNL2 and LMX1B, with certain Lmx1b mutations causing high IOP and glaucoma resembling POAG in mice. The newly identified loci increase the proportion of variance explained in each GERA race/ethnicity group, with the largest gain in African-Americans (0.5-3.1%). A meta-analysis combining GERA and UKB identifies 24 additional loci. Our study provides important insights into glaucoma pathogenesis.
Recommended Citation
Choquet H,
Paylakhi S,
Kneeland SC,
Thai K,
Hoffmann T,
Yin J,
Kvale M,
Banda Y,
Tolman N,
Williams PA,
Schaefer C,
Melles R,
Risch N,
John S,
Nair K,
Jorgenson E.
A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci. Nat Commun 2018 Jun 11; 9(1):2278