Exome Array Analysis of Nuclear Lens Opacity

Stephanie J. Loomis, Alison Klein, Kristine E. Lee, Fei Chen, Samantha Bomotti, Barbara Truitt, Sudha K. Iyengar, Ronald Klein, Barbara E.K. Klein, Priya Duggal

Research output: Contribution to journalArticle

Abstract

Purpose: Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. Methods: We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. Results: No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10–6; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10–5). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10–6) and among never smokers (N = 790, p = 2.67 × 10–6). Conclusions: This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalOphthalmic Epidemiology
DOIs
StateAccepted/In press - Nov 29 2017

Fingerprint

Exome
Cataract
Sclerosis
Genes
Gene Frequency
Smoking
Blindness
Lenses
Single Nucleotide Polymorphism
Rodentia
Regression Analysis

Keywords

  • exome array
  • genetics
  • nuclear cataract
  • nuclear lens opacity
  • Nuclear sclerosis

ASJC Scopus subject areas

  • Epidemiology
  • Ophthalmology

Cite this

Exome Array Analysis of Nuclear Lens Opacity. / Loomis, Stephanie J.; Klein, Alison; Lee, Kristine E.; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K.; Klein, Ronald; Klein, Barbara E.K.; Duggal, Priya.

In: Ophthalmic Epidemiology, 29.11.2017, p. 1-5.

Research output: Contribution to journalArticle

Loomis, SJ, Klein, A, Lee, KE, Chen, F, Bomotti, S, Truitt, B, Iyengar, SK, Klein, R, Klein, BEK & Duggal, P 2017, 'Exome Array Analysis of Nuclear Lens Opacity', Ophthalmic Epidemiology, pp. 1-5. https://doi.org/10.1080/09286586.2017.1406122
Loomis, Stephanie J. ; Klein, Alison ; Lee, Kristine E. ; Chen, Fei ; Bomotti, Samantha ; Truitt, Barbara ; Iyengar, Sudha K. ; Klein, Ronald ; Klein, Barbara E.K. ; Duggal, Priya. / Exome Array Analysis of Nuclear Lens Opacity. In: Ophthalmic Epidemiology. 2017 ; pp. 1-5.
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abstract = "Purpose: Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. Methods: We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. Results: No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10–6; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10–5). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10–6) and among never smokers (N = 790, p = 2.67 × 10–6). Conclusions: This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.",
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AU - Chen, Fei

AU - Bomotti, Samantha

AU - Truitt, Barbara

AU - Iyengar, Sudha K.

AU - Klein, Ronald

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N2 - Purpose: Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. Methods: We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. Results: No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10–6; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10–5). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10–6) and among never smokers (N = 790, p = 2.67 × 10–6). Conclusions: This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

AB - Purpose: Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. Methods: We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. Results: No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10–6; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10–5). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10–6) and among never smokers (N = 790, p = 2.67 × 10–6). Conclusions: This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

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