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Abstract #77911 Published in IGR 19-4
A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci
Choquet H; Paylakhi S; Kneeland SC; Thai KK; Hoffmann TJ; Yin J; Kvale MN; Banda Y; Tolman NG; Williams PA; Schaefer C; Melles RB; Risch N; John SWM; Nair KS; Jorgenson ENature communications 2018; 9: 2278
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), 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.
Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, 94612, USA.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
