scholarly journals RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) Gene Variants with Predisposition to Age-Related Macular Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Alvita Vilkeviciute ◽  
Loresa Kriauciuniene ◽  
Romanas Chaleckis ◽  
Vytenis Pranas Deltuva ◽  
Rasa Liutkeviciene
Keyword(s):  
Macular Degeneration ◽  
Association Studies ◽  
Strong Association ◽  
Age Related Macular Degeneration ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Exudative Amd ◽  
Age Related ◽  
Significant Difference ◽  
The Impact

Background. Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of a central part of the neural retina (macula) and a leading cause of blindness in elderly people. While it is known that the AMD is a multifactorial disease, genetic factors involved in lipid metabolism, inflammation, and neovascularization are currently being widely studied in genome-wide association studies (GWAS). The aim of our study was to evaluate the impact of new single nucleotide polymorphisms (SNPs) in RAD51B, TRIB1, COL8A1, and COL10A1 genes on AMD development. Methods. Case-control study involved 254 patients diagnosed with early AMD, 244 patients with exudative AMD, and 942 control subjects. The genotyping of RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) was carried out using TaqMan assays by a real-time polymerase chain reaction (RT-PCR) method. Results. Statistically significant difference was found in genotype (TT, TC, and CC) distribution of COL8A1 rs13095226 between exudative AMD and control groups (60.2%, 33.6%, and 6.1% vs. 64.9%, 32.3%, and 2.9%, respectively, p=0.036). Also, comparing with TT+TC, rs13095226 CC genotype was associated with 3.5-fold increased odds of exudative AMD development (OR = 3.540; 95% CI: 1.415-8.856; p=0.007). Conclusion. Our study revealed a strong association between a variant in COL8A1 (rs13095226) and exudative AMD development.

scholarly journals Haplotypes of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 Gene Polymorphisms in Age-Related Macular Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Greta Gedvilaite ◽  
Kriste Kaikaryte ◽  
Loresa Kriauciuniene
Keyword(s):  
Macular Degeneration ◽  
Protective Factor ◽  
Protective Role ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk ◽  
And Gender ◽  
The Impact

Background. To determine the impact of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 genotypes on the development of age-related macular degeneration (AMD) in the Lithuanian population. Methods. A total of 916 subjects were examined: 309 patients with early AMD, 301 patients with exudative AMD, and 306 healthy controls. The genotyping of HTRA1 rs11200638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 was carried out using the RT-PCR method. Results. Our study showed that single-nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative AMD, and the variant in KCTD10 (rs56209061) was found to be associated with decreased odds of early and exudative AMD development after adjustments for age and gender in early AMD analysis and after adjustments only for age in exudative AMD. The haplotype containing two minor alleles C-A and the G-A haplotype in rs3793784-rs11200638 were statistically significantly associated with an increased risk of exudative AMD development after adjustment for age, while the G-G haplotype showed a protective role against early and exudative AMD and the haplotype C-G in rs3793784-rs11200638 was associated with a decreased risk only of exudative AMD development. Conclusions. Our study identified two markers, rs11200638 and rs3793784, as risk factors for early and exudative AMD, and one marker, rs56209061, as a protective factor for early and exudative AMD development. The haplotypes constructed of rs3793784-rs11200638 were found to be associated with AMD development, as well.

Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Gene Polymorphisms ◽  
Age Related Macular Degeneration ◽  
Spanish Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

scholarly journals Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration

2015 ◽  
Author(s):  
Erin K. Wagner ◽  
Yi Yu ◽  
Eric H. Souied ◽  
Sanna Seitsonen ◽  
Ilkka J. Immonen ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Rare Variants ◽  
Association Studies ◽  
Low Frequency ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Meta Analyses

ABSTRACTAlthough >20 common frequency age-related macular degeneration (AMD) alleles have been discovered with genome-wide association studies, substantial disease heritability remains unexplained. In this study we sought to identify additional variants, both common and rare, that have an association with advanced AMD. We genotyped 4,332 cases and 25,268 controls of European ancestry from three different populations using the Illumina Infinium HumanExome BeadChip. We performed meta-analyses to identify associations with common variants and performed single variant and gene-based burden tests to identify associations with rare variants. Two protective, low frequency, non-synonymous variants A307V in PELI3 (odds ratio [OR]=0.14, P=4.3×10−10) and N1050Y in CFH (OR=0.76, Pconditional=1.6×10−11) were significantly associated with a decrease in risk of AMD. Additionally, we identified an enrichment of protective alleles in PELI3 using a burden test (OR=0.14). The new variants have a large effect size, similar to rare mutations we reported previously in a targeted sequencing study, which remain significant in this analysis: CFH R1210C (OR=18.82, P=3.5×10−07), C3 K155Q (OR=3.27, P=1.5×10−10), and C9 P167S (OR=2.04, P=2.8×10−07). We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8x10−07; Firth corrected OR = 0.64, P = 9.6x10−11). This study supports the involvement of both common and low frequency protective variants in AMD. It also may expand the role of the high-density lipoprotein pathway and branches of the innate immune pathway, outside that of the complement system, in the etiology of AMD.

scholarly journals Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Madhvi Menon ◽  
Shahin Mohammadi ◽  
Jose Davila-Velderrain ◽  
Brittany A. Goods ◽  
Tanina D. Cadwell ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Single Cell ◽  
Association Studies ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Genome Wide Association Studies ◽  
Human Retina ◽  
Age Related

Abstract Genome-wide association studies (GWAS) have identified genetic variants associated with age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. However, it has been challenging to identify the cell types associated with AMD given the genetic complexity of the disease. Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) of human retinas using two independent platforms, and report the first single-cell transcriptomic atlas of the human retina. Using a multi-resolution network-based analysis, we identify all major retinal cell types, and their corresponding gene expression signatures. Heterogeneity is observed within macroglia, suggesting that human retinal glia are more diverse than previously thought. Finally, GWAS-based enrichment analysis identifies glia, vascular cells, and cone photoreceptors to be associated with the risk of AMD. These data provide a detailed analysis of the human retina, and show how scRNA-seq can provide insight into cell types involved in complex, inflammatory genetic diseases.

scholarly journals Prioritization of Cancer-Related Genomic Variants by SNP Association Network

2015 ◽  
Vol 14s2 ◽  
pp. CIN.S17288
Author(s):  
Changning Liu ◽  
Zhenyu Xuan
Keyword(s):  
Association Studies ◽  
Age Related Macular Degeneration ◽  
Chromatin Interaction ◽  
Reference Database ◽  
Genome Wide Association Studies ◽  
Association Network ◽  
Nucleotide Polymorphisms ◽  
Gwas Study ◽  
Snp Association ◽  
Age Related

We have developed a general framework to construct an association network of single nucleotide polymorphisms (SNPs) (SNP association network, SAN) based on the functional interactions of genes located in the flanking regions of SNPs. SAN, which was constructed based on protein-protein interactions in the Human Protein Reference Database (HPRD), showed significantly enriched signals in both linkage disequilibrium (LD) and long-range chromatin interaction (Hi-C). We used this network to further develop two methods for predicting and prioritizing disease-associated genes from genome-wide association studies (GWASs). We found that random walk with restart (RWR) using SAN (RWR-SAN) can greatly improve the prediction of lung-cancer-associated genes by comparing RWR with the use of network in HPRD (AUC 0.81 vs 0.66). In a reanalysis of the GWAS dataset of age-related macular degeneration (AMD), SAN could identify more potential AMD-associated genes that were previously ranked lower in the GWAS study. The interactions in SAN could facilitate the study of complex diseases.

scholarly journals Genetic Mechanism Revealed of Age-Related Macular Degeneration Based on Fusion of Statistics and Machine Learning Method

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongyi Du ◽  
Ning Kong ◽  
Jibin Zhang
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Association Studies ◽  
Area Under The Curve ◽  
Gene Interaction ◽  
Age Related Macular Degeneration ◽  
Support Vector ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Causal Genes

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world which affects the quality of life for millions of elderly individuals worldwide. Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to AMD. To better understand the disease pathogenesis and identify causal genes for AMD, we applied random walk (RW) and support vector machine (SVM) to identify AMD-related genes based on gene interaction relationship and significance of genes. Our model achieved 0.927 of area under the curve (AUC), and 65 novel genes have been identified as AMD-related genes. To verify our results, a statistics method called summary data-based Mendelian randomization (SMR) has been implemented to integrate GWAS data and transcriptome data to verify AMD susceptibility-related genes. We found 45 genes are related to AMD by SMR. Among these genes, 37 genes overlap with those found by SVM-RW. Finally, we revealed the biological process of genetic mutations leading to changes in gene expression leading to AMD. Our results reveal the genetic pathogenic factors and related mechanisms of AMD.

Sign in / Sign up

Export Citation Format

Share Document