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X. Raymond Gao, Fangda Fan; Polygenic risk score is associated with intraocular pressure and improves glaucoma prediction in the UK Biobank cohort. Invest. Ophthalmol. Vis. Sci. 2018;59(9):779.
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Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Despite previous genome-wide association studies (GWASs) reporting a number of novel single nucleotide polymorphisms (SNPs) associated with IOP, these SNPs have limited ability for genomic prediction. Using large biobank cohorts has enabled increased accuracy for discovering SNPs for prediction. We constructed polygenic risk scores (PRSs) for intraocular pressure (IOP) using a big data approach to test whether the PRSs are associated with IOP and whether using them improves glaucoma prediction.
We conducted this study using 117,649 participants in the eye and vision component of the UK Biobank (UKB) cohort. All study subjects were 40 years of age and older. Over 800,000 genotyped and 92 million imputed single nucleotide polymorphisms (SNPs) were available in the dataset. We constructed weighted and unweighted PRSs for IOP using previously reported IOP SNPs and SNPs derived from the UKB data. We examined the association of the PRSs with IOP and glaucoma using linear and logistic regression, respectively. To quantify the discrimination of PRS on glaucoma, we used the area under the receiver operating characteristic curve (AUC). To avoid overfitting, we created independent training and testing datasets using cross-validation.
The weighted PRS was significantly associated with IOP (P = 3.80E-121), after adjusting for age, sex, and 10 principal components of genetic ancestry. The PRS explained 5% additional variance in IOP. The weighted PRS was also significantly associated with glaucoma (P = 9.10E-5) and improved AUC for glaucoma when added to the other covariates (AUC difference = 0.05). Subjects in the top quintile of IOP PRS were 4.25 (95% CI, 1.42 – 12.69, P = 0.0002) times likely to have glaucoma, compared with those in the bottom category. The unweighted PRS gave similar results, but with less significance. Investigation using the imputed data is ongoing and may further improve the model performance.
We determined that PRS is significantly associated with IOP and improves prediction of glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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