The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index; 2 of the 23 sources its claims cite were checked for support.
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration
Open accessAbstract
Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 × 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
Overview
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Written from the paper’s full text.
TL;DR
This large meta-analysis of genome-wide association studies for advanced age-related macular degeneration (AMD) identified two novel common susceptibility loci, near FRK/COL10A1 and VEGFA, and confirmed 10 previously reported loci. The findings implicate angiogenesis and extracellular collagen matrix pathways in advanced AMD.
Key findings
- rs1999930 near FRK/COL10A1 was associated with reduced risk of advanced AMD (combined OR 0.87, 95% CI 0.83–0.91, P = 1.1 × 10−8); rs4711751 near VEGFA was associated with increased risk (combined OR 1.15, 95% CI 1.10–1.21, P = 8.7 × 10−9).
- Ten previously reported loci were confirmed with genome-wide significant signals in the combined analysis, including ARMS2/HTRA1 (rs10490924, P = 3.6 × 10−322), CFH (rs1061170, P = 1.3 × 10−261; rs1410996, P = 7.4 × 10−235), CFB (rs641153, P = 5.5 × 10−31), C3 (rs2230199, P = 4.6 × 10−29), C2 (rs9332739, P = 2.4 × 10−23), CFI (rs10033900, P = 4.1 × 10−10), LIPC (rs10468017, P = 2.7 × 10−12), TIMP3 (rs9621532, P = 2.2 × 10−15), and CETP (rs3764261, P = 6.9 × 10−9).
- Both novel variants had similar effect sizes for geographic atrophy and neovascular AMD subtypes in the TMMG samples.
- A risk score using 14 validated or suggested variants estimated a >50-fold difference in advanced AMD risk between high-risk (score >2) and low-risk (score <−2) individuals; the associated loci explained ∼39% of total variance, or 55% of the heritability, of advanced AMD.
Methods
- Meta-analysis of GWAS in the TMMG data set: 2594 advanced AMD cases and 4134 controls of European ancestry, with 6,036,699 high-quality SNPs imputed using 1000 Genomes Project reference genotypes.
- Replication in 5640 cases and 52,174 controls from 10 independent cohorts; top signals were tested with fixed-effects meta-analysis, and heterogeneity was assessed by Cochran’s Q-test.
- Cases had advanced AMD (geographic atrophy or neovascular disease); controls were without macular degeneration. Analyses adjusted for genotyping platform and genetic ancestry principal components.
Limitations
- The paper states that discovery effect sizes for both novel SNPs were larger than replication effect sizes, possibly due to a “winner’s curse” phenomenon.
- The paper notes that the genome-wide significance threshold assumes ∼1,000,000 independent SNPs, but 1000 Genomes imputation tested many more correlated SNPs, and no empirical studies address genome-wide significance for 1000 Genomes-derived data.
- The paper states that the genetic risk score’s clinical utility needs further evaluation in independent samples, and that associations may exist for other endophenotypes such as macular drusen; evident from the text, all cohorts were of European ancestry, limiting generalizability, and not all replication cohorts contributed to every SNP analysis (e.g., Rotterdam Study was not genotyped for rs4711751).
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Statistics
Figures
![Figure 3. rs934080 in a putative CRX transcription factor-binding site. rs4711751 is in strong LD with rs934080, a variant which resides in a highly evolutionarily conserved region (UCSC genome browser) and disrupts a putative CRX transcription factor-binding site (CAA[T/C]C).](/paper-figures/727d7eaf019a49fdab35529c356c1454/common-variants-near-frk-col10a1-and-vegfa-are-associated-with-advanced-age-figure-3.jpg)
Verification
Claims the paper makes
25 Own result · 15 Own method · 14 Not checked yet · 6 Own interpretation · 3 No basis given · 1 Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The risk allele (T) of rs4711751 also had a similar magnitude of effect on GA [OR = 1.23 (1.08–1.40), P = 2.0 × 10−3] and NV [OR = 1.20 (1.09–1.32), P = 2.5 × 10−4].”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Using a standard liability threshold model (25), the previously reported loci combined with the new loci discovered in this study explain ∼39% of the total variance (or 55% of the heritability) of advanced AMD.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [25] Barrett, 2008, Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease, Nat. Genet. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“ARMS2/HTRA1 was more strongly related to NV compared with GA as previously reported (23).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
What the sources say
- Not checked yetcites [23] Sobrin, 2011, ARMS2/HTRA1 locus can confer differential susceptibility to the advanced subtypes of age-related macular degeneration, Am. J. Ophthalmol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, we observed highly statistically significant association signals at SNPs in six previously published loci, including ARMS2/HTRA1 (rs10490924, P = 1.2 × 10−144), CFH (rs1061170, P = 5.6 × 10−138, and rs1410996, P = 2.1 × 10−134), CFB (rs641153, P = 2.9 × 10−22), C3 (rs2230199, P = 1.4 × 10−18), C2 (rs9332739, P = 4.3 × 10−12), CFI (rs10033900, P = 2.4 × 10−11) and LIPC (rs1532085, P =”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plaincorrelationaln = 2,594 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD.”
- Also stated in: § RESULTS · plain
“Two other variants in ABCA1 (rs1883025, P = 1.2 × 10−7) and COL8A1 (rs13095226, P = 9.7 × 10−7) which were reported in our previous GWAS (15) are also still noteworthy candidates”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The risk locus rs1999930 associated with advanced AMD in our study is in strong LD (R2 = 0.81 in 1000 Genomes CEU data) with a functional variant rs9488843.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Association signals at CFH, C2, CFB, C3, CFI and ARMS2/HTRA1 were also significant for both GA and NV compared with controls.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study.”
- Also stated in: § DISCUSSION · boosted
“In addition, we confirmed strong association with the previously reported genetic variations at 10 loci including ARMS2/HTRA1 (rs10490924, P = 3.6 × 10−322), CFH (rs1061170, P = 1.3 × 10−261, and rs1410996, P = 7.4 × 10−235), CFB (rs641153, P = 5.5 × 10−31), C3 (rs2230199, P = 4.6 × 10−29), C2 (rs9332739, P = 2.4 × 10−23), CFI (rs10033900, P = 4.1 × 10−10), LIPC (rs10468017, P = 2.7 × 10−12), TIMP”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > Abstract
boostedcorrelationaln = 2,594- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § DISCUSSION · boosted
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The risk allele (T) at rs4711751 is on the same haplotype as the evolutionarily conserved allele (T) at rs943080.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Combining the effect sizes of all independent replication cohorts using a fixed effects model confirmed the association (OR = 0.90, P = 8.3 × 10−4).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plaincorrelationaln = 5,640 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Probably not a substantial claim. 21
- It may state two separate claims as one. 14
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“All samples included in this study met quality control measures as described previously (15,16).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
What the sources say
- Supportedcites [15] Neale, 2010, Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC), Proc. Natl Acad. Sci. USA source
The citation points to previously described quality-control measures, not to independent verification of the citing study’s samples. In Methods (Genotyping, Analysis, and Replication; page unavailable), the source describes its QC filters and the exclusion of individuals with low call rates; Results (Case and Control Sample Development; page unavailable) also reports stringent sample quality control. (LLM, conf=0.88)
- Supportedcites [16] Chen, 2010, Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration, Proc. Natl Acad. Sci. USA source
The Results and Discussion section describes quality-control exclusions for individuals and genetic markers and reports a 99.94% average call rate for analyzed markers and samples. The Genotyping and Imputation section also states that standard quality filters were applied. These passages support the citation to previously described quality-control measures; whether every sample in the citing study passed them is the citing authors’ own assertion. (LLM, conf=0.88)
plainn = 6,728- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The T allele of rs4711751, with an allele frequency of 0.54 in cases and 0.50 in controls, was associated with increased risk of advanced AMD [OR = 1.21 (95% CI:1.11–1.32)].”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 10−9)”
- Also stated in: § RESULTS · plain
“This SNP reached genome-wide significance [OR = 1.15 (95% CI: 1.10–1.21), P = 8.7 × 10−9] in the combined analysis”
- Also stated in: § DISCUSSION · plain
“We also identified a novel locus (rs4711751, P = 8.7 × 10−9) for advanced AMD near VEFGA.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The allele (G) at rs9488843, which creates a possible transcription factor-binding site for paired box 3 (PAX3) near the promoter region of COL10A1, is on the same haplotype as the allele (T) at rs1999930.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, we note that the newly identified SNP rs4711751 is in strong LD with rs943080 (R2 = 1.0 in 1000 Genomes CEU data), a variant that resides in a highly evolutionarily conserved region (Fig. 3).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, rs4711751 is in moderate LD with nearby genome-wide significant variants reported in type 2 diabetes, waist–hip ratio and chronic kidney disease (R2= 0.31, D′ = 0.91 to rs881858).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, rs881858 was not significantly associated with advanced AMD in the TMMG meta-analysis (P = 0.11) and cannot explain the association we observe in rs4711751.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the merged data set of TMMG contained 6728 samples, of which 4300 were genotyped by AFFY 6.0 and 2428 were genotyped by ILMN 370.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plainn = 6,728- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The replication data sets consisted of 5640 cases and 52 174 controls from 10 independent cohorts from JHU, COL, Genentech, Iceland, Wash-U, AUS, RS, FR-CRET, Irish and an independent replication sample from Tufts/MGH.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plainn = 5,640- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The TMMG meta-analysis data set consisted of: (i) 1242 cases and 492 controls from the Tufts/MGH GWAS Cohort Study (15), which were derived from ongoing AMD study protocols as described previously (8,15,24,35–37); (ii) 1355 cases and 1076 controls from the MMAP Cohort Study (16); (iii) 1188 controls from the (MIGen) Consortium Study (21) and (iv) 1378 controls from the GAIN Schizophrenia Study (22”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [15] Neale, 2010, Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC), Proc. Natl Acad. Sci. USA source
- Not checked yetcites [16] Chen, 2010, Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration, Proc. Natl Acad. Sci. USA source
- Not checked yetcites [21] Kathiresan, 2009, Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants, Nat. Genet. source
plainn = 1,242- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The effect sizes of both rs1999930 and rs4711751 in the replication cohorts are smaller than the effect sizes estimated in the TMMG analysis.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, SNP rs4711751 appears to be independent of the rs2010963 variant (R2 = 0.015, D′ = 0.14 in samples of European ancestry); therefore, the association we identified near VEGFA was in a novel region and is not likely due to LD with SNPs in the VEGFA promoter region.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > Abstract
hedgedconditionaln = 2,594- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A consensus set of 6 036 699 high-quality SNPs from each imputed data set was analyzed by PLINK, using a generalized linear model controlling for the genotyping platform and genetic ancestry based on principal component analysis.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our novel findings are not likely caused by population admixture or population substructure, because subjects in all cohorts are of European ancestry, and we adjusted for the genetic ancestry components in our study.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The top 40 SNPs were validated using Sequenom genotyping on 1600 samples that were also part of the Tufts/MGH GWAS.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plainn = 1,600- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In patients with osteoarthritis, expression of COL10A1 was significantly downregulated (28).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [28] Lamas, 2010, Large-scale gene expression in bone marrow mesenchymal stem cells: a putative role for COL10A1 in osteoarthritis, Ann. Rheum. Dis. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“cone–rod homeobox (CRX), which is an essential transcription factor highly expressed in RPE and retinal ganglion cells (27).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [27] Corbo, 2010, CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors, Genome Res. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All replication studies applied the same criteria for the diagnosis of cases.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plainn = 5,640- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A major advantage of the study design is the careful diagnosis of cases across all cohorts.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we only included imputed genotypes of common variants (MAF >0.01) in the analysis”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“As this prediction model only included genetic risk factors, we expect an improvement of the performance of advanced AMD risk assessment with additional environmental and demographic factors in prospective studies as in our previous calculations (18,19).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [18] Seddon, 2011, Risk models for progression to advanced age-related macular degeneration using demographic, environmental, genetic, and ocular factors, Ophthalmology source
- Not checked yetcites [19] Seddon, 2009, Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables, Invest. Ophthalmol. Vis. Sci. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the meta-analysis of GWAS, we included only imputed genotypes with imputation quality scores >0.6, where the score is defined as the ratio-of-variances (empirical/asymptotic) of each genotype.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The larger effect size observed in the discovery cohort (TMMG) could be due to a ‘winner's curse’ phenomenon where association is often exaggerated relative to the estimated effect in follow-up studies (34).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [34] Lohmueller, 2003, Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease, Nat. Genet. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The sample size of this study is the largest of all published association studies for advanced AMD to date.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the two SNPs we selected for replication in FRK/COL10A1 locus, rs12204816 failed the genotyping quality criteria in the replication phase, but rs1999930 was successfully genotyped in all 10 replication cohorts.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This score is commonly applied as a quality filter for imputed genotypes and is equivalent to the RSQR_HAT value by MACH and the information content (INFO) measure by PLINK (44).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [44] de Bakker, 2008, Practical aspects of imputation-driven meta-analysis of genome-wide association studies, Hum. Mol. Genet. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The genetic loci associated with AMD suggest that the disease process may be explained in part by dysregulation of the alternative complement pathway (CFH, C2, CFB, C3, CFI), HDL cholesterol metabolism (LIPC, CETP, ABCA1), angiogenesis (VEGFA) and degradation of extracellular matrix (COL10A1, COL8A1, FRK, TIMP3, and possibly ARMS2).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Owing to the larger size of the Icelanders data set, the imputation is more reliable based on the Icelanders data set than the imputation based on the HapMap or 1000 Genomes Project.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > MATERIALS AND METHODS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with other complex diseases, the associated risk variants for advanced AMD are more informative in terms of predicting risk of disease.”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“The newly identified SNP (rs4711751) is 60 kb downstream of VEGFA and >90 kb away from a SNP (rs2010963) in the VEGFA promoter region which has been reported to be associated with AMD (26).”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
What the sources say
- Not checked yetcites [26] Haines, 2006, Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6, Invest. Ophthalmol. Vis. Sci. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
There are no empirical studies that address levels of genome-wide significance for 1000 Genomes Project-derived data.
“To our knowledge, there are no empirical studies that address levels of genome-wide significance for the 1000 Genomes Project-derived data.”
The paper relies on this without support.
The generally accepted genome-wide significance threshold of P < 5 × 10−8 is appropriate for this study despite the larger number of SNPs tested.
“For this study, we utilized the generally accepted genome-wide level of significance (P < 5 × 10−8) as our threshold for association.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Association has also been demonstrated with several additional loci14–20, each providing an entry-point into AMD biology and potential therapeutic targets.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
“rs4711751 is in strong LD with rs943080 (R2 = 1.0 in 1000 Genomes CEU data)”
§ Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration > DISCUSSION
“Figure 3. rs934080 in a putative CRX transcription factor-binding site. rs4711751 is in strong LD with rs934080”
Citations
Cites
1 retracted
Sudhakar, A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24813 · Cited by 162
RetractedPLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · cited 4×
“SNPs which met genotype quality control criteria in other replication cohorts were tested for association with advanced AMD, using a generalized linear model in PLINK.”
MethodInfluentialSelf-citationPrincipal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
METAL: fast and efficient meta-analysis of genomewide association scans
Willer, C. J., Li, Y., & Abecasis, G. R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq340 · Cited by 5,205 · cited 1×
“The P-value for the combined analysis was derived from the effect size estimates and standard errors, using a fixed effects model by METAL (51).”
MethodComplement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492
Endostatin: an endogenous inhibitor of angiogenesis and tumor growth
O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birkhead, J. R., Olsen, B. R., & Folkman, J. (1997) · Cell · doi:10.1016/s0092-8674(00)81848-6 · Cited by 4,486
Howie, B. N., Donnelly, P., & Marchini, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000529 · Cited by 3,928 · cited 1×
“For candidate SNPs not directly genotyped in the Genentech samples, genotype information was imputed using IMPUTE version 2 (48) with combined reference data of CEU and TSI population from the 1000 Genomes Project (June 2010 release) and HapMap3 Project.”
MethodBrowning, S. R., & Browning, B. L. (2007) · The American Journal of Human Genetics · doi:10.1086/521987 · Cited by 3,217
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., et al. (2008) · Nature Genetics · doi:10.1038/ng.175 · Cited by 2,593 · cited 1×
“Using a standard liability threshold model (25), the previously reported loci combined with the new loci discovered in this study explain 39% of the total variance (or 55% of the heritability) of advanced AMD.”
MethodSelf-citation
Cited by
Sorted by citations
Items 201–253 of 253
Feng, L., Chen, S., Dai, H., Dorajoo, R., Liu, J., Kong, J., Yin, X., & Ren, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.696885 · Cited by 5
“However, the missense mutation Y402H (rs1061170) of CFH, which is a strong risk variant for AMD (Zareparsi et al., 2005; Yu et al., 2011) did not show any association effect in our CSC cohort, although our samples provide sufficient statistical power (>80”
BackgroundWang, J.-H., Urrutia-Cabrera, D., Mora, S. M., Nguyen, T., Hung, S., Hewitt, A. W., Edwards, T. L., & Wong, R. C. B. (2020) · doi:10.1101/2020.07.10.198143 · Cited by 4
“[5] Yu Y, Bhangale TR, Fagerness J, Ripke S, Thorleifsson G, Tan PL, et al.”
BackgroundGenetics in Age-Related Macular Degeneration
Broadhead, G., Chang, A., & McCluskey, P. (2012) · Asia-Pacific Journal of Ophthalmology · doi:10.1097/apo.0b013e31826e1d4a · Cited by 4
Sam, J., Reble, E., Kodida, R., Shaw, A., Clausen, M., Salazar, M., Shickh, S., Mighton, C. E., Carroll, J. C., Armel, S. R., et al. (2022) · Human Genetics · doi:10.1007/s00439-022-02466-5 · Cited by 6
“The manifestation of common diseases, such as agerelated macular degeneration and Crohn’s disease, is largely dependent on both genetic and environmental risk factors (Yu et al. 2011; Franke et al. 2010); thus, the 5-tier ACMGAMP classification standards do not apply to these common disease risk SNPs.”
BackgroundSalman, A., McClements, M. E., & MacLaren, R. E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031697 · Cited by 4
Čebatorienė, D., Vilkevičiūtė, A., Gedvilaitė, G., Duseikaitė, M., Bruzaite, A., Kriaučiūnienė, L., Žaliūnienė, D., & Liutkevičienė, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179750 · Cited by 4
“…connections, and gaining insights into the molecular mechanisms underlying AMD are some of the major outcomes of whole exome studies in AMD, as ARMS2 , VEGFA , TNFRSF [84–86], and IL1B1 were selected based on association with the pathogenetic mechanism of the chronic inflammatory process [87].”
BackgroundThe Relationship Between Hepatic Lipase Gene Variant and Advanced Age-Related Macular Degeneration
Lou, L., Hu, K., Jin, K., Zhang, S., & Ye, J. (2014) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2014.1752 · Cited by 3
Humanes Leukozytenantigensystem in der Augenheilkunde
Lapp, T., Reinhold, D., Böhringer, D., & Reinhard, T. (2013) · Der Ophthalmologe · doi:10.1007/s00347-013-2861-7 · Cited by 3
Epidemiology and Risk Factors for Age-Related Macular Degeneration
Seddon, J. M., & Sobrin, L. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4557-0737-9.00063-1 · Cited by 3
Self-citationHamzić, E., Spahić, L., Pištoljević, N., Dzanko, E., Pašić, S., Kadrić, L., Serdarević, F., & Hajdarpašić, A. (2024) · Biomolecules and Biomedicine · doi:10.17305/bb.2024.10221 · Cited by 3
“Patients with macular degeneration have been observed to have problems with face perception [39].”
BackgroundHuang, L., Zhang, X., Tam, P. O. S., Chen, H., Hao, F., Pang, C., Wen, F., & Yang, Z. (2018) · Journal of Human Genetics · doi:10.1038/s10038-018-0490-3 · Cited by 3
Huang, L., Li, M., Ma, X., Li, Y., Zhang, C., Sun, Y., Bai, Y., Wang, B., Yu, W., Zhao, M., et al. (2014) · Ophthalmic Research · doi:10.1159/000362763 · Cited by 3
Genetic factors for idiopathic choroidal neovascularization
Cao, X., Peng, X., You, Q. S., Liu, F., Ding, Y., & Yang, H. (2019) · Ophthalmic Genetics · doi:10.1080/13816810.2019.1630844 · Cited by 3
Li, Y., Fu, J., Liu, J., Feng, H., & Chen, X. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/3787567 · Cited by 3
Seddon, J. M., De, D., Grunenkovaite, L., & Ferrara, D. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.14.31 · Cited by 2
Self-citationThe Role of Inflammation in Age-Related Macular Degeneration
Harris, J. M., & Wu, D. M. (2025) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000578 · Cited by 2
Alagappan, L. P., Ramaswamy, Y., Sundaramoorthy, D. K., Bhaskar, J., Sarangapani, S., Sen, P., Raman, R., Bhende, M. P., & Mathavan, S. (2022) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-022-05861-w · Cited by 2
Paradigm of Susceptibility Genes in AMD and PCV
Riaz, M., & Baird, P. N. (2017) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-4-431-56511-6_14 · Cited by 2
Self-citationDevelopments in Ocular Genetics
Whigham, B. T., & Allingham, R. R. (2013) · Asia-Pacific Journal of Ophthalmology · doi:10.1097/apo.0b013e318294b837 · Cited by 2
“Future studies with increased sample size and power are expected to identify loci of more modest impact.(55) Eventually, a more complete understanding of risk factors may have diagnostic utility.”
BackgroundMutations in MERTK are not associated with age-related macular degeneration
Al-khersan, H., Kwong, A. M., & Grassi, M. A. (2018) · International Ophthalmology · doi:10.1007/s10792-017-0789-7 · Cited by 2
“Heterozygous SNPs in the TIMP Metallopeptidase Inhibitor 3 (TIMP3) gene increase the risk of developing AMD while more severe mutations in this same gene cause Sorsby fundus dystrophy [10, 11].”
Harmonization of Study and Reference Data by PhaseLift: Saving Time When Imputing Study Data
Gorski, M., Winkler, T. W., Stark, K. J., Müller‐Nurasyid, M., Ried, J. S., Grallert, H., Weber, B. H. F., & Heid, I. M. (2014) · Genetic Epidemiology · doi:10.1002/gepi.21812 · Cited by 1
“For detailed presentations, the CFH locus [Yu et al., 2011] on chromosome 1 (chr1:196,594,399 to 196,718,099 on b37.”
Dóra, S. J., Marika, T., Doró, Z., Nagymihály, R., Josifovska, N., Facskó, A., & Goran, P. (2014) · SZTE Publicatio Repozitórium (University of Szeged) · Cited by 1
Genome-Wide Association Study of Age-Related Eye Diseases in Chinese Population
Chen, L. J., Rong, S. S., & Pang, C. P. (2017) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-4-431-56511-6_16 · Cited by 1
Wie groß sind die kleinen genetischen Risiken?
Heid, I. M., Winkler, T. W., Graßmann, F., & Weber, B. H. F. (2011) · Medizinische Genetik · doi:10.1007/s11825-011-0295-7 · Cited by 1
Age-Related Macular Degeneration and Vision Impairment
Wright, C. B., & Ambati, J. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_16 · Cited by 1
Elhamamsy, M., Souka, A., Assi, H. E., Ashraf, M., & Kassem, H. S. (2017) · Middle East Journal of Medical Genetics · doi:10.1097/01.mxe.0000512347.39933.9c · Cited by 1
“…in several different ethnic and racial groups: Caucasians, Americans, Russians, Indians, and Eastern Asians (Japanese and Chinese) (Fisher et al., 2005; Rivera et al., 2005; Conley et al., 2006; Dewan et al., 2006; Kanda et al., 2007; Arakawa et al., 2011; Yu et al., 2011; Hu et al., 2015).”
BackgroundGenetics of Age-Related Macular Degeneration in Asia
Yamashiro, K. (2021) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-15-9184-6_6 · Cited by 1
Abid, G., Messal, A., Harmel, M., Idder, A., Fodil, M., & Fodil, M. (2022) · PubMed Central · doi:10.22099/mbrc.2022.43634.1743 · Cited by 1
“This association was also confirmed in meta-analysis GWAS in a European ancestry sample [8].”
ResultGenetic markers for age-related macular degeneration
Wong, C. W., & Cheng, C. (2014) · doi:10.2217/fmeb2013.13.255 · Cited by 1
Age Related Macular DegenerationPreprint
Dufies, M. (2020) · doi:10.32545/encyclopedia202007.0005.v3
Fagerness, J. A., Yu, Y., Maller, J., Neale, B. M., Reynolds, R. C., Daly, M. J., & Seddon, J. M. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.177
Self-citationRetinal oximetry and age-related macular degeneration
Geirsdóttir, Á. (2015) · Skemman
The Role of Nutrition in Age-Related Eye Diseases
Gopinath, B. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00032-7
Patil, R. V., Cheng, C., Cheung, C. M. G., & Wong, T. Y. (2017) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-4-431-56511-6_37
Introducing Johanna M. Seddon, the 2017 Recipient of the Mildred Weisenfeld Award
Jager, M. J. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-23542
Khandhadia, S., Gibson, J., Ennis, S., Cree, A. J., & Lotery, A. J. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.02.014
Molecular Genetics of Macular Degeneration
Bailey, J. N. C., & Haines, J. L. (2016) · Wiley eBooks · doi:10.1002/9780470015902.a0021445
Segregation, linkage, GWAS, and sequencing
Waksmunski, A. R., Main, L. R., & Haines, J. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816222-4.00002-2
de Almeida, L. N. F. (2012) · Americanae (AECID Library)
Wiggs, J. L. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-382227-7.00091-4
Dry Age-Related Macular Degeneration
Makhijani, V. S., Ung, C., & Husain, D. (2020) · Retina atlas · doi:10.1007/978-981-15-3001-2_1
Wagner, E. K., Yu, Y., Souied, E. H., Seitsonen, S., Immonen, I. J. R., Häppölä, P., Raychaudhuri, S., Daly, M. J., & Seddon, J. M. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/034173
Self-citationContributions of Promoter Variants to Complex Eye Diseases
Ng, T. K., & Pang, C. P. (2021) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-15-9184-6_19
Arshinoff, S. A. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718046008.793480995
Macular Degeneration, Age Related
Haim, L. N. B., Duncan, J. L., & Zayit‐Soudry, S. (2021) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0029296
Analysis of hypertension predictors using multivariate models through the lens of aging processes
Zelenskaya, Е. М., Panarina, A. Y., Лукинов, В. Л., Александровна, С. А., & Израйлевна, Л. Г. (2025) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2025-6546
Buitendijk, G. H. S., Springelkamp, H., Ho, L., & Klaver, C. C. W. (2013) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-3-642-36324-5_5
Self-citationBruzaite, A., Vilkevičiūtė, A., Čebatorienė, D., Žaliūnienė, D., Čiapienė, I., Smalinskienė, A., Kriauciuniene, L., & Liutkevičienė, R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083697
“Additionally, alterations in collagen-related genes, including COL8A1 and COL10A1 [21,24], have been implicated in the pathogenesis of AMD, thereby supporting the relevance of investigating other collagen genes associated with the extracellular matrix, such as COL2A1 .”
The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD)
Hyttinen, J. M. T., Salminen, A., Kauppinen, A., & Kaarniranta, K. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118114
Rapid, HIF-1α-independent, response of VEGF secretion to decreased O 2 in mouse retina
Kamat, V., Grumbine, M. K., Bao, K., Tsumura, L., Lim, R. R., Wang, S., Hermansson, J., Kramlich, J., den Hartigh, L. J., Chao, J. R., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2602872123
Molecular investigations of age-related macular degeneration
Whitmore, S. S., Anderson, M. G., Sohn, E. H., Scheetz, T. E., Tan, K., & Mullins, R. F. (2015) · doi:10.17077/etd.7xzjf8nh
Metadata
- Authors
- Yu, Y., Bhangale, T. R., Fagerness, J., Ripke, S., Thorleifsson, G., Tan, P. L., Souied, E. H., Richardson, A. J., Merriam, J. E., Buitendijk, G. H. S., Reynolds, R., Raychaudhuri, S., Chin, K. A., Sobrin, L., Evangelou, E., Lee, P. H., Lee, A. Y., Leveziel, N., Zack, D. J., Campochiaro, B., Campochiaro, P., Smith, R. T., Barile, G. R., Guymer, R. H., Hogg, R., Chakravarthy, U., Robman, L. D., Gustafsson, O., Sigurdsson, H., Ortmann, W., Behrens, T. W., Stefansson, K., Uitterlinden, A. G., van Duijn, C. M., Vingerling, J. R., Klaver, C. C. W., Allikmets, R., Brantley, M. A., Baird, P. N., Katsanis, N., Thorsteinsdottir, U., Ioannidis, J. P. A., Daly, M. J., Graham, R. R., & Seddon, J. M.
- Affiliations
- Tufts University (US)
- Broad Institute (US)
- Duke University (US)
- Université Paris-Est Créteil (FR)
- The University of Melbourne (AU)
- Columbia University (US)
- Tufts Medical Center (US)
- Massachusetts Eye and Ear Infirmary (US)
- Washington University in St. Louis (US)
- Institut de la Vision (FR)
- Johns Hopkins University (US)
- Queen's University Belfast (GB)
- Genentech (US)
- Erasmus MC (NL)
- Corresponding author
- Seddon, Johanna M.
- ORCID
- Yu, Yi
- Bhangale, Tushar R.
- Ripke, Stephan
- Tan, Perciliz L.
- Souied, Eric H.
- Buitendijk, Gabriëlle H.S.
- Raychaudhuri, Soumya
- Sobrin, Lucia
- Lee, Phil H.
- Lee, Aaron Y.
- Leveziel, Nicolas
- Zack, Donald J.
- Campochiaro, Peter
- Smith, R. Theodore
- Guymer, Robyn H.
- Hogg, Ruth
- Chakravarthy, Usha
- Ortmann, Ward
- Behrens, Timothy W.
- Uitterlinden, André G.
- Vingerling, Johannes R.
- Klaver, Caroline C.W.
- Allikmets, Rando
- Brantley, Milam A.
- Baird, Paul N.
- Katsanis, Nicholas
- Ioannidis, John P.A.
- Daly, Mark J.
- Graham, Robert R.
- Seddon, Johanna M.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-10
- Volume
- 20
- Issue
- 18
- Pages
- 3699-3709
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3159552
- OpenAlex
- W2099989980
- Semantic Scholar
- 97301598fe7bc85d8c49c0c3a586fa1ead9afa0e
- Cited by
- 254
- References
- 54
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 12 · 2021: 14 · 2020: 10 · 2019: 18 · 2018: 7 · 2017: 15 · 2016: 23 · 2015: 27 · 2014: 32 · 2013: 41 · 2012: 27
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- Research to Prevent Blindness
- Brigham and Women's Hospital
- Tufts Medical Center
- Macula Vision Research Foundation
- Northwestern University
- Massachusetts Lions Eye Research Fund
- State Government of Victoria
- National Institutes of Health (5k12ey016335-17, K12EY16335, RO1-EY11309)
- Tufts University School of Medicine
- Medical Research Council
- National Health and Medical Research Council (529923)
- National Institute of Mental Health (MH59566, R01 MH61675, U01-MH79470, MH-60870, R01 MH-59571, R01MH59588, U01MH46276, R01-MH59566, R01-MH60879, U01MH046276, R01-MH60870, MH-59586, R01-MH59586, R01MH059566, MH79470, MH60879, R01 MH81800, R01MH59587, U01MH046318, R01-MH59565, MH81800, R01MH059571, MH 61675, R01MH060879, R01MH059565, U01MH46289, MH67257, MH46289, R01MH081800, R01 MH-67257, MH46318, R01MH060870, U01MH079469, R01MH061675, R01MH059586, MH59571, R01MH059588, R01MH067257, U01MH079470, MH59588, MH79469, U01MH46318, MH-59587, MH59565, R01MH059587, MH-46276, U01MH-79469)
- National Eye Institute (K12 EY16335, EY-017404, R01EY013435, R01 EY13435, EY16335, EY-13435, K12-EY016335, R01 EY 11309, EY11309, P30EY001765, R01EY011309, R24EY017404)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR055688)
- Alcon Research Institute
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- advanced age-related macular degeneration, genetic susceptibility, common genetic variants, VEGF-A, angiogenesis, collagen matrix, complement factor H, complement system, hepatic lipase, TIMP-3, cholesteryl ester transfer protein, ABCA1, COL8A1, genetic loci
- MeSH terms
- Female, Genotype, Humans, Macular Degeneration, Male, Neoplasm Proteins, Protein-Tyrosine Kinases, Genetic Variation, Cohort Studies, Case-Control Studies, Polymorphism, Single Nucleotide, Collagen Type X, Vascular Endothelial Growth Factor A, White People, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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