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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.

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Related in: MedlinePlus

Quantile-quantile (Q-Q) plot for age and sex-adjusted genome-wide association of corneal astigmatism.
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f1: Quantile-quantile (Q-Q) plot for age and sex-adjusted genome-wide association of corneal astigmatism.

Mentions: No loci in the TEST/BATS or Raine populations attained genome-wide significance (p<5×10−8). Additionally, following meta-analysis on >2.5M overlapping genotyped and imputed SNPs, no locus reached the level of genome-wide significance (Figure 1 and Figure 2). Eleven loci had a nominal threshold of suggestive significance (p<1×10−5). Table 3 shows details regarding the ten most significant SNPs following the meta-analysis.


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)

Quantile-quantile (Q-Q) plot for age and sex-adjusted genome-wide association of corneal astigmatism.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Quantile-quantile (Q-Q) plot for age and sex-adjusted genome-wide association of corneal astigmatism.
Mentions: No loci in the TEST/BATS or Raine populations attained genome-wide significance (p<5×10−8). Additionally, following meta-analysis on >2.5M overlapping genotyped and imputed SNPs, no locus reached the level of genome-wide significance (Figure 1 and Figure 2). Eleven loci had a nominal threshold of suggestive significance (p<1×10−5). Table 3 shows details regarding the ten most significant SNPs following the meta-analysis.

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