A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci

被引：117

作者：

Choquet, Helene ^{[1
]}

Paylakhi, Seyyedhassan ^{[2
]}

Kneeland, Stephen C. ^{[3
]}

Thai, Khanh K. ^{[1
]}

Hoffmann, Thomas J. ^{[4
,5
]}

Yin, Jie

Kvale, Mark N.

Banda, Yambazi ^{[4
]}

Tolman, Nicholas G. ^{[3
]}

Williams, Pete A. ^{[3
]}

Schaefer, Catherine ^{[1
]}

Melles, Ronald B. ^{[6
]}

Risch, Neil ^{[1
,4
,5
]}

John, Simon W. M. ^{[3
]}

Nair, K. Saidas ^{[2
,7
]}

Jorgenson, Eric ^{[1
]}

机构：

[1] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA

[2] Univ Calif San Francisco, Sch Med, Dept Ophthalmol, San Francisco, CA 94143 USA

[3] Howard Hughes Med Inst, Jackson Lab, Bar Harbor, ME 04609 USA

[4] UCSF, Inst Human Genet, San Francisco, CA 94143 USA

[5] UCSF, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

[6] KPNC, Dept Ophthalmol, Redwood City, CA 94063 USA

[7] UCSF, Sch Med, Dept Anat, San Francisco, CA 94143 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

NAIL-PATELLA SYNDROME; GENETIC EPIDEMIOLOGY RESEARCH; HUMAN TRABECULAR MESHWORK; SOLUBLE ADENYLYL-CYCLASE; 1ST GLOBAL APPROVAL; AGING GERA COHORT; INTRAOCULAR-PRESSURE; GENOTYPE IMPUTATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS;

D O I：

10.1038/s41467-018-04555-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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.

引用

页数：14