Exome Array Analysis of Nuclear Lens Opacity

• Published in: Ophthalmic epidemiology 2018-05, Vol.25 (3), p.215-219
• Main Authors: Loomis, Stephanie J., Klein, Alison P., Lee, Kristine E., Chen, Fei, Bomotti, Samantha, Truitt, Barbara, Iyengar, Sudha K., Klein, Ronald, Klein, Barbara E. K., Duggal, Priya
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Cataract - diagnosis; Cataract - genetics; Cataract - metabolism; DNA - genetics; Exome - genetics; exome array; Female; Follow-Up Studies; Gene Frequency; genetics; Genotype; Humans; Male; Middle Aged; nuclear cataract; nuclear lens opacity; Nuclear sclerosis; Polymorphism, Single Nucleotide; Retrospective Studies
• ISSN: 0928-6586; 1744-5086
• DOI: 10.1080/09286586.2017.1406122

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