Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma

Abstract

Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide. Both IOP and POAG are highly heritable. We report a combined analysis of participants from the UK Biobank (n = 103,914) and previously published data from the International Glaucoma Genetic Consortium (n = 29,578) that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported. We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve head morphology. In 1,734 people with advanced glaucoma and 2,938 controls, participants in the top decile of the allele score were at increased risk (odds ratio (OR) = 5.6; 95% confidence interval (CI): 4.1-7.6) of glaucoma relative to the bottom decile.

Genome-Wide Association Study and Selection Signatures Detect Genomic Regions Associated with Seed Yield and Oil Quality in Flax

“…However, the development of such populations requires careful planning and time. Natural populations that possess tremendous phenotypic diversity can be advantageous in genome-wide association study (GWAS) with various molecular markers in plants and animals [26,27,28,29,30,31]. Association mapping using a diverse germplasm panel overcomes the phenotypic diversity limitation of bi-parental populations, thereby increasing the QTL mapping power [32] but is impeded by low detection power of association of rare alleles.…”

A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease

“…POAG is highly heritable 4,5 , and previous genome-wide association studies (GWAS) have identified important loci associated with POAG risk and IOP [6][7][8][9][10][11][12][13][14] . Despite this success, the POAG genetic landscape remains incomplete and identification of novel risk loci is required to further define contributing disease mechanisms that could be targets of novel preventative therapies.…”

Genome wide-association study identifies novel loci in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study

“…20 This remaining 10% is due to variants with small individual effect sizes in genes such as MYOC, OPTN, WDR36, CDK2N2B-AS1, TMC01, SIX6, ABCA1, GAS7, FOXC1, NTF4, ASB10, EFEMP1, and IL20RB. [20][21][22][23] However, most of these loci do not replicate in African Americans. The majority were discovered in populations of European, [24][25][26][27][28] Chinese 29 , and Japanese [30][31][32][33][34] descent or large meta-analyses of these groups, 23,28,35 and have greatly reduced or unknown role in African Americans.…”