Pharmacogenomics of steroid-induced ocular hypertension: relationship to high-tension glaucomas and new pathophysiologic insight
Song, Z.; Pany, S.; Guo, S.; Mazumder, A. G.; Itakura, T.; Huang, J.; Magarychoff, E.; Gurinovich, A.; Benchek, P. H.; Price, F. W.; Stamer, W. D.; Willoughby, C. E.; Senthilkumari, S.; George, R. J.; Chitipothu, S.; Lass, J. H.; Iyengar, S. K.; Schwartz, S. G.; Griswold, A. J.; Sebastiani, P. J.; Price, M. O.; Fini, M. E.
Show abstract
Adverse drug reactions are a frequent cause of worldwide morbidity and mortality. Glucocorticoids (GCs), commonly used to treat inflammatory diseases, alter gene expression with both beneficial and adverse consequences. When used in the eye, GCs cause steroid-induced ocular hypertension (SIOH) in 30-50% of patients, leading to steroid-induced glaucoma. Evidence suggests that predisposition to SIOH is genetically determined. Here we took a pharmacogenomic approach to discover DNA variants associated with SIOH. We identified 44 SNPs of genome-wide significance (p<5E-08) located at 26 risk loci out of a total of 531 SNPs of suggestive significance (p<5E-06) at 262 risk loci. Unlike SNPs identified in complex disease which are overwhelmingly common in frequency, most SNPs found here were rare or of low frequency, likely discoverable because of their large effect sizes. Follow-up analyses provide insight into the pathogenetic relationship of SIOH to high-tension glaucomas and suggest a new mechanistic paradigm for SIOH pathophysiology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=134 HEIGHT=200 SRC="FIGDIR/small/25333245v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@18a68daorg.highwire.dtl.DTLVardef@1e9f96borg.highwire.dtl.DTLVardef@1f61519org.highwire.dtl.DTLVardef@e335ef_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The 5-HT1A receptor antagonist WAY-100635 maleate reprograms metabolism to promote RGC differentiation and regeneration in retino-visual centers 92%
- Sex-specific transcriptome similarity networks elucidate comorbidity relationships 90%
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration 90%
Similar papers in this journal
- Pleiotropy method identifies genetic overlap between orofacial clefts at multiple loci from GWAS of multi-ethnictrios 92%
- Transcriptomic comparison of two selective retinal cell ablation paradigms in zebrafish reveals shared and cell-specific regenerative responses 91%
- Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation 91%
Similar papers in this journal
- Whole-exome sequencing study identifies novel rare variants and genes associated with intraocular pressure and glaucoma 95%
- A Proteogenomic Signature of Age-related Macular Degeneration in Blood 93%
- The contribution of common regulatory and protein-coding TYR variants in the genetic architecture of albinism 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.