Limits...
Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.

Yazar S, Mishra A, Ang W, Kearns LS, Mountain JA, Pennell C, Montgomery GW, Young TL, Hammond CJ, Macgregor S, Mackey DA, Hewitt AW - Mol. Vis. (2013)

Bottom Line: Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry.Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009.Better-powered studies are required to validate the novel putative findings of our study.

View Article: PubMed Central - PubMed

Affiliation: Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia. seyhanyazar@lei.org.au

ABSTRACT

Purpose: Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry.

Methods: Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis.

Results: Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009.

Conclusions: Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.

Show MeSH

Related in: MedlinePlus

Locus-specific plots of the most significant single nucleotide polymorphisms (SNPs) in this study. These plots display the most significant result in the meta-analysis genome-wide association study (GWAS). The locus identified by Fan et al. Chromosome 4q12 (A) and two loci identified in this study Chromosome 12p11 (B) and 3q13 (C) are shown. SNPs are plotted as the –log10 of the p value.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3675057&req=5

f3: Locus-specific plots of the most significant single nucleotide polymorphisms (SNPs) in this study. These plots display the most significant result in the meta-analysis genome-wide association study (GWAS). The locus identified by Fan et al. Chromosome 4q12 (A) and two loci identified in this study Chromosome 12p11 (B) and 3q13 (C) are shown. SNPs are plotted as the –log10 of the p value.

Mentions: We found no evidence for replication of the PDGFRA locus (Figure 3). In our cohorts, the previously reported top SNP in this region (rs7677751) was not significantly associated with corneal astigmatism (beta=–0.0423, standard deviation error=0.0423; p=0.32). The minor allele frequency of rs7677751 was 0.133 and 0.123 in the Raine study and the TEST/BATS, respectively. The top SNP at this locus was rs6821576 (p=0.003).


Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.

Yazar S, Mishra A, Ang W, Kearns LS, Mountain JA, Pennell C, Montgomery GW, Young TL, Hammond CJ, Macgregor S, Mackey DA, Hewitt AW - Mol. Vis. (2013)

Locus-specific plots of the most significant single nucleotide polymorphisms (SNPs) in this study. These plots display the most significant result in the meta-analysis genome-wide association study (GWAS). The locus identified by Fan et al. Chromosome 4q12 (A) and two loci identified in this study Chromosome 12p11 (B) and 3q13 (C) are shown. SNPs are plotted as the –log10 of the p value.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675057&req=5

f3: Locus-specific plots of the most significant single nucleotide polymorphisms (SNPs) in this study. These plots display the most significant result in the meta-analysis genome-wide association study (GWAS). The locus identified by Fan et al. Chromosome 4q12 (A) and two loci identified in this study Chromosome 12p11 (B) and 3q13 (C) are shown. SNPs are plotted as the –log10 of the p value.
Mentions: We found no evidence for replication of the PDGFRA locus (Figure 3). In our cohorts, the previously reported top SNP in this region (rs7677751) was not significantly associated with corneal astigmatism (beta=–0.0423, standard deviation error=0.0423; p=0.32). The minor allele frequency of rs7677751 was 0.133 and 0.123 in the Raine study and the TEST/BATS, respectively. The top SNP at this locus was rs6821576 (p=0.003).

Bottom Line: Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry.Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009.Better-powered studies are required to validate the novel putative findings of our study.

View Article: PubMed Central - PubMed

Affiliation: Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia. seyhanyazar@lei.org.au

ABSTRACT

Purpose: Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry.

Methods: Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis.

Results: Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009.

Conclusions: Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.

Show MeSH
Related in: MedlinePlus