Dataset Information

Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups.

ABSTRACT:

Background

The prevalence of age-related macular degeneration (AMD) varies from 6.8 to 18.3% for all forms of AMD and from 0.6 to 2.6% for late AMD according to race, suggesting the existence of genetic differences among races. The purpose of this study was to determine the genetic causes of differences in the prevalence of AMD among individuals of different races.

Methods

We collected 138 AMD-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact tests to assess whether the effect allele at a given SNP was significantly enriched or depleted in the database.

Results

European, American, and South Asian populations showed similar heatmap patterns, whereas East Asian, and Korean populations had distinct patterns. Korean populations exhibited patterns that were different from those of the other groups; rs5754227 (SYN3), rs1626340 (TGFBR1/COL15A1), rs3750846(ARMS2/HTRA1), and rs9564692 (B3GALTL) were enriched, whereas rs2230199 (C3) and rs73036519 (EXOC3L2/MARK4) were depleted in Koreans; these SNPs are associated with late AMD. The genetic risk score calculated from allele frequencies was not less in East Asians than in Europeans.

Conclusion

The prevalence of AMD is lower in Asians than in Europeans. However, our study showed that genetic risk scores in East Asians were similar to those in Europeans, which may explain why the global projected number of people with AMD by 2040 is in largest for East Asians, including Koreans.

SUBMITTER: Shin HT

PROVIDER: S-EPMC7898441 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups.

Shin Hyun-Tae HT Yoon Byung Woo BW Seo Je Hyun JH

BMC ophthalmology 20210222 1

<h4>Background</h4>The prevalence of age-related macular degeneration (AMD) varies from 6.8 to 18.3% for all forms of AMD and from 0.6 to 2.6% for late AMD according to race, suggesting the existence of genetic differences among races. The purpose of this study was to determine the genetic causes of differences in the prevalence of AMD among individuals of different races.<h4>Methods</h4>We collected 138 AMD-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies ...[more]

PMID: 33618707

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Project description:Single-nucleotide polymorphisms (SNPs) associated with the CFH, ARMS2, C3, LIPC, CFB, and C2 genes are associated with age-related macular degeneration (AMD); however, the association of these SNPs with angiographic features of neovascular AMD has been inconsistent in previous studies, and to date, no studies have addressed their association with features on optical coherence tomography.To evaluate the influence of genotype of SNPs previously associated with AMD on the phenotype of neovascular lesions.Participants for this cross-sectional study were recruited from the 1185 patients enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), a randomized clinical trial. Eligibility criteria for CATT specified that eyes have choroidal neovascularization and visual acuity between 20/25 and 20/320. A subgroup of 835 patients provided blood samples from July 2010 through September 2011 and were genotyped for the SNPs rs1061170 (CFH), rs10490924 (ARMS2),rs2230199 (C3), rs10468017 (LIPC), rs4151667 (CFB), rs547154 (C2) using TaqMan SNP genotyping assays. Data analysis was initiated in November 2013 and completed in January 2016.Pretreatment ocular characteristics on fluorescein angiography (lesion type, area of neovascularization and total lesion, retinal angiomatous proliferation) and on time-domain optical coherence tomography (presence of intraretinal, subretinal, and subretinal pigment epithelium fluid; thickness at the foveal center of the retina, subretinal fluid, and subretinal tissue complex), visual acuity, and age.A total of 835 (73%) of 1150 CATT patients were genotyped. Mean age decreased with the number of risk alleles for CFH (P < .001), ARMS2 (P < .001), and C3 (P = .005). The following results were found as the number of risk alleles increased from 0 to 1 to 2. For CFH, mean total thickness decreased from 476 to 476 to 434 µm (P?=?.01; adjusted for age, sex, and smoking status). For ARMS2, the mean area of the total lesion increased from 2.0 to 2.8 to 2.4 mm2 (P?=?.03), the proportion with retinal angiomatous proliferation lesions increased from 8% to 10% to 12% (P?=?.05), and the proportion with intraretinal fluid increased from 72% to 71% to 82% (P?=?.008). For C3, the proportion with intraretinal fluid decreased from 78% to 69% to 64% (P?=?.001), and the mean retinal thickness decreased from 225 to 207 to 197 µm (P?=?.02).CFH, ARMS2, and C3 were associated with specific features of neovascularization at the time patients were enrolled in CATT. Previously identified associations of ARMS2 and CFH with type of choroidal neovascularization on fluorescein angiography were not confirmed. New associations with OCT features identified in CATT need confirmation to establish whether a true association exists.clinicaltrials.gov Identifier: NCT00593450.

Project description:PurposeTenomodulin (TNMD) is located in the X-chromosome encoding a putative angiogenesis inhibitor which is expressed in retina. Associations of single nucleotide polymorphisms of TNMD with the prevalence of age-related macular degeneration (AMD) were examined.MethodsSix markers covering 75% of the common sequence variation in the coding region of TNMD and 10 kb up- and downstream were genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18 men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All participants were over 65 years old and did not have diabetes mellitus. Due to the chromosomal locus, the association of genotypes with AMD was assessed genderwise.ResultsThree markers, rs1155974, rs2073163, and rs7890586, were associated with a risk of AMD in women. In comparison to women with other genotypes, the women who were homozygous for the minor allele (genotypes rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk for having AMD, respectively. These differences were due to the unequal prevalence of exudative AMD. In comparison to women who were homozygous for the major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021 in additive model; p=0.022 in recessive model) for exudative AMD, and the women with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038 in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype had a significantly smaller risk for having AMD than women with the other genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low frequency of this genotype, this finding must be interpreted cautiously. The false discovery rate was <10% for all of the aforementioned results.ConclusionsOn the basis of the putative antiangiogenic role of TNMD and the present genetic associations of TNMD with AMD in women, we suggest that TNMD could be a novel candidate gene for AMD. These results should be confirmed in further studies.

Project description:Importance:Previous studies investigating the association of single-nucleotide polymorphisms (SNPs) that confer increased risk of age-related macular degeneration (AMD) with pseudodrusen have yielded conflicting results and have not evaluated other AMD SNPs or pseudodrusen subtypes. Objective:To determine the association of SNPs in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), HtrA serine peptidase 1 (HTRA1), complement C2 (C2), complement C3 (C3), lipase C (LIPC), and complement factor B (CFB) genes with the presence of pseudodrusen and pseudodrusen subtypes (ie, dot, reticular, and confluent). Design, Setting, and Participants:In this post hoc analysis of cross-sectional data from US participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs rs1061170 (Y402H variant in CFH), rs800292 (I62V variant in CFH), rs10490924 (A69S variant in ARMS2), rs11200638 (HTRA1), rs547154 (C2), rs2230199 (R102G variant in C3), rs10468017 (LIPC), and rs4151667 (L9H variant in CFB). Main Outcomes and Measures:Presence and subtype of baseline pseudodrusen in either eye determined using color fundus photography, red-free images, and fluorescein angiograms. Results:Among 835 participants enrolled for genotyping, 755 (90.4%) were evaluated for pseudodrusen. Of these, 471 (62.4%) were female and 750 (99.3%) were white, and the mean (SD) age was 78.3 (7.5) years. A total of 213 of 755 participants (28.2%) had pseudodrusen (107 [14.2%] had dot pseudodrusen, 180 [23.8%] had reticular pseudodrusen, and 102 [13.5%] had confluent pseudodrusen). After adjusting for age, sex, and smoking status, the ARMS2 risk allele T was associated with higher risk of pseudodrusen (odds ratio [OR], 1.93; 95% CI, 1.19-3.12) for TT vs GG (P?=?.04). A similar association was found for HTRA1 (OR, 2.04; 95% CI, 1.26-3.31) for AA vs GG (P?=?.03). The CFH Y402H risk allele C was associated with lower risk of pseudodrusen (OR, 0.61; 95% CI, 0.38-0.97) for CC vs TT but was not statistically significant after correcting for multiple comparison (P?=?.20). CFH Y402H, ARMS2, HTRA1, and C3 were significantly associated with reticular pseudodrusen. Conclusions and Relevance:Among patients with neovascular AMD, the AMD risk alleles ARMS2 and HTRA1 were associated with an increased risk of pseudodrusen and the risk allele CFH Y402H was associated with lower risk of pseudodrusen, supporting findings from previous studies. Understanding the role of these SNPs in the development of pseudodrusen might improve our understanding of the pathogenesis of AMD and help develop future therapies.

Dataset Information

Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups.

Background

Methods

Results

Conclusion

Publications

Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups.

Similar Datasets

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