Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population

Huang, Lulin; Chen, Yuhong; Lin, Ying; Tam, Peter; Cheng, Yilian; Shi, Yi; Gong, Bo; Lü, Fang; Yang, Jialiang; Wang, Haixin; Yin, Yi; Cao, Yunshan; Jiang, Dan; Zhong, Ling; Bai, Xue; Wang, Jing; Fang, Hao; Lee, Dean-Yao; Pang, Chi‐Pui; Sun, Xinghuai; Yang, Zhenglin

doi:10.1007/s11427-018-9430-2

Cited by 21 publications

(9 citation statements)

References 51 publications

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“…The study of genetic factors closely related to IOP can simultaneously provide new insights into the genetic mechanism of glaucoma and new directions and methods for the clinical diagnosis and treatment of glaucoma. A GWAS showed that βII spectrin expression is an eye-related phenotype 141 that is also closely related to IOP 142 . The relationship between βII spectrin and IOP revealed in this study not only increased our understanding of biomarkers in IOP but also provided important insights into the genetic markers of glaucoma and will provide future genetic screening and treatment methods for glaucoma related to IOP.…”

Section: βIi Spectrin In Eye Diseasesmentioning

confidence: 99%

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Yang¹,

Yang²,

Sun³

et al. 2021

Int. J. Biol. Sci.

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βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

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Section: βIi Spectrin In Eye Diseasesmentioning

confidence: 99%

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Yang¹,

Yang²,

Sun³

et al. 2021

Int. J. Biol. Sci.

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“…Mining glaucoma genes. The search included mutation/association genes, as well as IOP genes for glaucoma genetic factors [42][43][44] . The search identified 159 genes in the OMIM database, 144 genes in the GWAS catalog (before 06/20/2017), and 86 genes in the Phenolyzer database.…”

Section: Resultsmentioning

confidence: 99%

“…Glaucoma is a set of disorders that cause damage to the optic nerve and worsen over time. Pathological ocular hypertension, race, a family history of glaucoma, vasospasms, and peripheral vascular disease are common contributing factors 46 www.nature.com/scientificreports www.nature.com/scientificreports/ research reported that various pathways, including focal adhesion, extracellular matrix-receptor interaction, cancer, and the PI3K-Akt pathway, were significantly related to IOP 43 , pointing to its complex etiology. Current glaucoma medications reduce IOP by reducing the production of fluid in the eye or increasing its outflow.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive map of disease networks and molecular drug discoveries for glaucoma

Wang

Deng

Wan

et al. 2020

Sci Rep

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Glaucoma is the leading cause of irreversible blindness worldwide. the molecular etiology of glaucoma is complex and unclear. At present, there are few drugs available for glaucoma treatment. The aim of the present study was to perform a systematic analysis of glaucoma candidate drugs/chemicals based on glaucoma genes, including genetic factors and differentially expressed (DE) genes. In total, 401 genes from the genetic databases and 1656 genes from the DE gene analysis were included in further analyses. In terms of glaucoma-related genetic factors, 54 pathways were significantly enriched (FDR < 0.05), and 96 pathways for DE genes were significantly enriched (FDR < 0.05). A search of the PheWAS database for diseases associated with glaucoma-related genes returned 1,289 diseases, and a search for diseases associated with DE glaucoma-related genes returned 1,356 diseases. Cardiovascular diseases, neurodegenerative diseases, cancer, and ophthalmic diseases were highly related to glaucoma genes. A search of the DGIdb, KEGG, and CLUE databases revealed a set of drugs/chemicals targeting glaucoma genes. A subsequent analysis of the electronic medical records (EMRs) of 136,128 patients treated in Sichuan provincial people's Hospital for candidate drug usage and the onset of glaucoma revealed nine candidate drugs. Among these drugs, individuals treated with nicardipine had the lowest incidence of glaucoma. Taken together with the information from the drug databases, the 40 most likely candidate drugs for glaucoma treatment were highlighted. Based on these findings, we concluded that the molecular mechanism of glaucoma is complex and may be a reflection of systemic diseases. A set of ready-to-use candidate drugs targeting glaucoma genes may be developed for glaucoma clinical drug treatments. Our results provide a systematic interpretation of glaucoma genes, interactions with other systemic diseases, and candidate drugs/chemicals. Glaucoma is a set of progressive optic neuropathies 1 and the leading cause of irreversible blindness worldwide 2. Glaucoma is characterized by a loss of retinal ganglion cells and consequent visual field loss. The two most common forms of glaucoma are primary open-angle glaucoma (POAG) and primary angle-closure glaucoma 3. The main known risk factors for glaucoma include high intraocular pressure (IOP), older age, African race, high myopia 4 , a high vertical cup/intervertebral disc ratio 5 , and a reduction in the optic disk area and central corneal thickness 6. Epidemiological studies have shown that the prevalence of glaucoma is expected to reach 76 million by 2020 and 118 million globally by 2040 due to population aging 7. The mechanism underlying the development of glaucoma is not fully understood. Glaucoma is a complex hereditary disease. Mutations in the OPTN, MYOC, and WDR36 genes have been identified as the causes of POAG 8. Thus far, 14 genome-wide association studies have identified 97 single-nucleotide polymorphisms near 75 genes associated with glaucoma in the GWAS catalog, includi...

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“…A genetic variant in VKORC1L1 (rs11763147) was found to be associated with CCT in a combined meta-analysis of the European and the Asian samples (4.0 × 10 − 9 , 15]. Another genetic variant (rs10563220) located upstream of VKORC1L1 was found to be significantly associated with intraocular pressure in a GWAS of 8552 Chinese participants [ 41 ]. More studies are needed to elucidate the exact functions of VKORC1L1 in association with CCT, and explore whether/how it is involved in the pathogenesis of POAG and keratoconus.…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analysis identified genes pleiotropically associated with central corneal thickness

Yang

Liu

et al. 2021

BMC Genomics

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Objective To prioritize genes that were pleiotropically or potentially causally associated with central corneal thickness (CCT). Methods We applied the summary data-based Mendelian randomization (SMR) method integrating summarized data of genome-wide association study (GWAS) on CCT and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with CCT. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analyses were done for participants of European and East Asian ancestries, separately. Results We identified multiple genes showing pleiotropic association with CCT in the participants of European ancestry. CLIC3 (ILMN_1796423; PSMR = 4.15 × 10− 12), PTGDS (ILMN_1664464; PSMR = 6.88 × 10− 9) and C9orf142 (ILMN_1761138; PSMR = 8.09 × 10− 9) were the top three genes using the CAGE eQTL data, and RP11-458F8.4 (ENSG00000273142.1; PSMR = 5.89 × 10− 9), LCNL1 (ENSG00000214402.6; PSMR = 5.67 × 10− 8), and PTGDS (ENSG00000107317.7; PSMR = 1.92 × 10− 7) were the top three genes using the GTEx eQTL data. No genes showed significantly pleiotropic association with CCT in the participants of East Asian ancestry after correction for multiple testing. Conclusion We identified several genes pleiotropically associated with CCT, some of which represented novel genes influencing CCT. Our findings provided important leads to a better understanding of the genetic factors influencing CCT, and revealed potential therapeutic targets for the treatment of primary open-angle glaucoma and keratoconus.

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Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population

Cited by 21 publications

References 51 publications

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

A comprehensive map of disease networks and molecular drug discoveries for glaucoma

Mendelian randomization analysis identified genes pleiotropically associated with central corneal thickness

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