Abstract
Purpose :
Despite numerous studies, the reasons for development of strabismus are not yet clear. We performed a genome-wide association study to investigate genetic risk factors for strabismus.
Methods :
We analysed unrelated UK Biobank participants of white British ancestry (n= 66,694) who responded to the questionnaire item, “Why were glasses/contact lenses prescribed?” and underwent an eye examination during their assessment. A total of 1,345 (2.0%) of these participants reported ‘squint or a turn in an eye since childhood’ as one of the reasons for wearing glasses or contact lenses. Association between self-reported strabismus and genetic polymorphisms were tested, including as covariates: sex, age, the presence/absence of amblyopia, genotyping array (UK Biobank Axiom array or UK BiLEVE array), and the first 10 principal components. A GWAS was carried out for 7,469,170 imputed variants, using Firth regression in PLINK 2.0. Replication was carried out in the paediatric ALSPAC cohort for clinician-diagnosed strabismus at age 7 years-old (116 cases and 5084 controls).
Results :
Genetic variants at a single locus, the TSPAN10-NPLOC4-PDE6G gene region, reached genome-wide significance for association with strabismus. Lead variant rs75078292 (OR=1.26, P=2.24E-08) was in perfect or almost perfect linkage disequilibrium with approximately 20 other variants, of which two were predicted to have functions effect: (1) rs6420484 substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene; (2) 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The association of rs75078292 with strabismus was independent of refractive error, and minimally affected after adjustment for self-reported amblyopia. The association with strabismus was replicated in the paediatric cohort (OR=1.85, P=0.009).
Conclusions :
We identified the novel genetic locus for strabismus. This study suggests functional variants in TSPAN10 confer susceptibility to strabismus.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.