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Series GSE201236 Query DataSets for GSE201236
Status Public on Apr 25, 2022
Title Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. It is associated with 23 multiple disease processes with primary open angle glaucoma (POAG) being the most prevalent. Due to its 24 complex, multifactorial nature, genetic predisposition is not completely understood thus, there is an urgent 25 need for additional investigations into the genetic regulation of IOP. Heterogenous stock (HS) outbred rats are 26 a multigenerational outbred population derived from eight inbred strains that have been fully sequenced. This 27 population is ideal for genome-wide association studies (GWAS) due to the accumulated recombinations 28 among well-defined haplotypes, the relatively high allele frequencies, access to a large collection of tissue 29 samples, and the large allelic effect size compared to human studies. The purpose of this study was to identify 30 genetic loci underlying elevated IOP using HS rats. Both male and female HS rats (N=1,812) were used in the 31 study. Genotyping-by-sequencing was used to obtain ~3.5M single nucleotide polymorphisms from each 32 individual. We performed a GWAS for the IOP phenotype using a linear mixed model and used permutation to 33 determine a genome-wide significance threshold. We also estimated SNP heritabilities. Our GWAS results 34 identified three genome-wide significant loci for elevated IOP on chromosomes 1, 5, and 16. These loci 35 contained 7 genes in total including Tyr, Grm5, Ctsc, Rab38, MGC94199, Plekhf2, and Csmd1. We also 36 mapped expression quantitative trait loci (eQTLs) in HS rat eye tissue and discovered a cis-eQTL for Ctsc 37 among our significant loci. Tyr is the only gene that has been previously associated with human IOP. This 38 study highlights the efficacy of HS rats for investigating the genetics of elevated IOP and identifying potential 39 candidate genes for future functional testing. In summary, GWAS using HS rats is a powerful method for 40 identifying genome regions that harbor variants responsible for the variation in quantitative traits, such as IOP. 41 Additional studies are ongoing to further narrow the list of candidate genes in these intervals.
Overall design mRNA profiles from the eye tissue of 53 HS rats
Contributor(s) Fowler S, Wang T, Munro D, Chitre A, Hollingsworth TJ, Garcia Martinez A, St. Pierre C, Bimschleger H, Gao J, Cheng R, Mohammadi P, Chen H, Polesskaya O, Palmer AA, Jablonski MM
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Submission date Apr 21, 2022
Last update date Apr 25, 2022
Contact name Daniel Munro
Organization name UC San Diego
Department Psychiatry
Lab Palmer Lab
Street address 9500 Gilman Drive
City La Jolla
State/province CA
ZIP/Postal code 92093
Country USA
Platforms (1)
GPL25947 Illumina NovaSeq 6000 (Rattus norvegicus)
Samples (53)
GSM6053242 00077E7BAA
GSM6053243 00077E8978
GSM6053244 00077E9993
BioProject PRJNA830468

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Supplementary file Size Download File type/resource
GSE201236_Eye.expr.log2.bed.gz 2.4 Mb (ftp)(http) BED
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Processed data are available on Series record

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