Caucasian families exhibit significant linkage of Myopia to chromosome 11p

Anthony M. Musolf, Claire Simpson, Bilal A. Moiz, Kyle A. Long, Laura Portas, Federico Murgia, Elise B. Ciner, Dwight Stambolian, Joan E. Bailey-Wilson

Research output: Contribution to journalArticle

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Abstract

Purpose. Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. METHODS. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. RESULTS. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. CONCLUSIONS. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

Original languageEnglish (US)
Pages (from-to)3547-3554
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number9
DOIs
StatePublished - Jan 1 2017

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Myopia
Chromosomes
Single Nucleotide Polymorphism
Genotype
Exome
Intergenic DNA
Genetic Loci
Refractive Errors
Penetrance
Information Storage and Retrieval
Vision Disorders
Microsatellite Repeats
Haplotypes
Genes
Genome
Phenotype

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Musolf, A. M., Simpson, C., Moiz, B. A., Long, K. A., Portas, L., Murgia, F., ... Bailey-Wilson, J. E. (2017). Caucasian families exhibit significant linkage of Myopia to chromosome 11p. Investigative Ophthalmology and Visual Science, 58(9), 3547-3554. https://doi.org/10.1167/iovs.16-21271

Caucasian families exhibit significant linkage of Myopia to chromosome 11p. / Musolf, Anthony M.; Simpson, Claire; Moiz, Bilal A.; Long, Kyle A.; Portas, Laura; Murgia, Federico; Ciner, Elise B.; Stambolian, Dwight; Bailey-Wilson, Joan E.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 9, 01.01.2017, p. 3547-3554.

Research output: Contribution to journalArticle

Musolf, AM, Simpson, C, Moiz, BA, Long, KA, Portas, L, Murgia, F, Ciner, EB, Stambolian, D & Bailey-Wilson, JE 2017, 'Caucasian families exhibit significant linkage of Myopia to chromosome 11p', Investigative Ophthalmology and Visual Science, vol. 58, no. 9, pp. 3547-3554. https://doi.org/10.1167/iovs.16-21271
Musolf, Anthony M. ; Simpson, Claire ; Moiz, Bilal A. ; Long, Kyle A. ; Portas, Laura ; Murgia, Federico ; Ciner, Elise B. ; Stambolian, Dwight ; Bailey-Wilson, Joan E. / Caucasian families exhibit significant linkage of Myopia to chromosome 11p. In: Investigative Ophthalmology and Visual Science. 2017 ; Vol. 58, No. 9. pp. 3547-3554.
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abstract = "Purpose. Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. METHODS. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90{\%} penetrance and 10{\%} phenocopy rate were performed. RESULTS. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. CONCLUSIONS. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.",
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T1 - Caucasian families exhibit significant linkage of Myopia to chromosome 11p

AU - Musolf, Anthony M.

AU - Simpson, Claire

AU - Moiz, Bilal A.

AU - Long, Kyle A.

AU - Portas, Laura

AU - Murgia, Federico

AU - Ciner, Elise B.

AU - Stambolian, Dwight

AU - Bailey-Wilson, Joan E.

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N2 - Purpose. Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. METHODS. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. RESULTS. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. CONCLUSIONS. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

AB - Purpose. Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. METHODS. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. RESULTS. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. CONCLUSIONS. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

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