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

Hv, Gudiseva; Ss, Verma; Vrm, Chavali; Rj, Salowe; Lucas, Anastasia; Dw, Collins; Rathi, Sonika; He, Jian‐Qing; Lee, Richard; Merriam, Sayaka; As, Bowman; Cp, McHugh; Mc, Zody; Pistilli, Maxwell; Khachataryan, Naira; Daniel, Ebenezer; Murphy, Windell; Weiner, Michael W.; Henderer, Jeffrey; Ross, Ahmara G.; Qn, Cui; Addis,; Lehman, Amanda; Miller-Ellis, Eydie; Ps, Sankar; Varma, Rohit; Williams, Scott M.; Ying, Gui‐Shuang; Jh, Moore; Ritchie,; Jm, O’Brien

doi:10.1101/2020.02.27.968156

Cited by 10 publications

(25 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent GWAS studies demonstrated that LMX1B variants are associated with elevated IOP and POAG, even without a diagnosis of NPS or extraocular involvement, and in the absence of anterior segment abnormalities [9]. Interestingly, in our Primary Open-Angle African American Glaucoma Genetics (POAAGG) GWAS study, the variants in LMX1B were significantly associated with mean deviation (MD) baseline, but not with IOP [13]. There have been relatively few studies specifically investigating the genetic risk factors for glaucoma in African American populations, even though this population has a higher prevalence of POAG and more severe outcomes [14,15].…”

Section: Introductionmentioning

confidence: 70%

“…The genotypes of the LMX1B gene were generated by using Illumina MEGA array chip. Data generation, quality control, and single variant associations' tests were performed as described in the POAAGG GWAS [13]. In brief, the genotype calls were generated using the Genome Studio genotyping module (GT).…”

Section: Genotypingmentioning

confidence: 99%

“…Phenotypic data for POAG cases were extracted from the REDCap Database, and glaucoma cases were grouped for analysis by LMX1B SNP genotype (e.g., GG and GC), which have previously been described by our group [13]. Genotype was masked during chart review for data extraction.…”

Section: Deep Phenotyping Of Casesmentioning

confidence: 99%

See 2 more Smart Citations

LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study

Meer

Qin

Gudiseva

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and has been associated with multiple genetic risk factors. The LMX1B gene is a genetic susceptibility factor for POAG, and several single-nucleotide polymorphisms (SNPs) were shown to be associated with POAG in our own prior Primary Open-Angle African American Glaucoma Genetics (POAAGG) study genome-wide association study (GWAS). This study evaluated the association of the LMX1B locus with baseline optic disc and clinical phenotypic characteristics of glaucoma patients from our African American cohort. Compared to the GG genotype in SNP rs187699205, the GC genotype in this SNP was found to be significantly associated with a smaller cup-to-disc ratio (CDR) and increased (better) visual field mean deviation (MD) in glaucoma cases. None of the glaucoma cases with the GC genotype had disc hemorrhages, disc notching, or beanpot disc appearance. In conclusion, glaucoma phenotypes differed significantly by LMX1B variant in African American patients with POAG, and a SNP variant was associated with certain disease features considered lower risk.

show abstract

Section: Introductionmentioning

confidence: 70%

Section: Genotypingmentioning

confidence: 99%

See 1 more Smart Citation

LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study

Meer

Qin

Gudiseva

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…[22] This study identified a genetic variation known as a single nucleotide polymorphism (SNP) involved in the homeostasis of the trabecular meshwork. [23] The trabecular meshwork (TM) is located in the anterior portion of the eye and regulates the outflow of the aqueous humor into circulation. [24] If resistance increases in the TM during aqueous humor outflow, intraocular pressure may rise leading to ocular hypertension.…”

Section: Genetic Influence On Ocular Hypertensionmentioning

confidence: 99%

Ocular Hypertension in Blacks

Laroche¹,

Rickford²

2021

Ocular Hypertension - The Knowns and Unknowns

View full text Add to dashboard Cite

Ocular hypertension occurs when intraocular pressure (IOP) is greater than the normal range with no evidence of vision loss or damage to the optic nerve. Individuals with ocular hypertension have an increased risk for glaucoma. The mean normal IOP is 15 mmHg and the mean IOP of untreated glaucoma is 18 mmHg. Elevated IOP commonly occurs in patients over the age of 50 and is often due to enlargement of the lens, narrowing of the angle, iridolenticular apposition, and pigment liberation that obstructs the trabecular meshwork. Cataract surgery and lensectomy can lower IOP and reduce the risk of glaucoma. The global wealth inequality of Blacks has created health inequities that have led to decreased access to surgical care contributing to higher rates of blindness from glaucoma. Greater education on the benefits of early cataract surgery and trabecular bypass for higher risk patients, as well as addressing wealth and health inequities, can help to bend the curve of blindness from glaucoma.

show abstract

“…The diagnosis of POAG was based on patients having an open iridocorneal angle along with characteristic glaucomatous optic nerve findings corresponding to visual field loss. Blood and saliva samples from the subjects were collected in heparinized vacutainers (BD Biosciences, San Jose, CA, USA) by venipuncture with prior written informed consent and were immediately transferred to the laboratories in ice containers for genetic analysis [32].…”

Section: Enrollment Of the Study Subjectsmentioning

confidence: 99%

Molecular Genetics and Functional Analysis Implicate CDKN2BAS1-CDKN2B Involvement in POAG Pathogenesis

Rathi

Danford

Gudiseva

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

The genes in the 9p21 locus (CDKN2B-AS1 & CDKN2B) are widely associated with Primary open-angle glaucoma (POAG). However, the functional importance of this locus in POAG pathogenesis is still unexplored. This study investigated the role of CDKN2BAS1-CDKN2B axis in POAG. We observed significant association of CDKN2B-AS1 SNP rs4977756 with POAG and its endophenotypic traits (vertical cup-disc ratio (p = 0.033) and central corneal thickness (p = 0.008)) by screening African American POAG cases (n = 1567) and controls (n = 1600). A luciferase reporter assay in Human embryonic kidney 293T (HEK293T) cells revealed that the region surrounding rs4977756 likely serves as a transcriptional repressor. siRNA-mediated knockdown of CDKN2B-AS1 in HEK293T cells and trabecular meshwork (TM) cells resulted in significantly increased expression of CDKN2B, which was also observed in human POAG ocular tissues. Pathway focused qRT-PCR gene expression analysis showed increased cellular senescence, TGFβ signaling and ECM deposition in TM cells after CDKN2B-AS1 suppression. In conclusion, we report that CDKN2B-AS1 may act as a regulator, and it could function by modulating the expression of CDKN2B. In addition, increase in CDKN2B levels due to CDKN2B-AS1 suppression may result in the senescence of trabecular meshwork cells leading to POAG pathogenesis.

show abstract

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

Cited by 10 publications

References 99 publications

LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study

LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study

Ocular Hypertension in Blacks

Molecular Genetics and Functional Analysis Implicate CDKN2BAS1-CDKN2B Involvement in POAG Pathogenesis

Contact Info

Product

Resources

About