GeneSet Information

Tier III GS409688 • cis-eQTL related to intraocular pressure (IOP) in hetergenous stock (HS) outbred rats_pvalue

DESCRIPTION:

All independent cis-eQTLs that were identified in RNA from 51 eye samples, for GWAS for intraocular pressure (IOP), that is, conditionally independent cis-eQTLs at 0.05 FDR threshold. For some genes, more than one eQTL was found using stepwise regression. In cases of multiple top SNPs with identical p-values (due to identical genotypes in the cohort) for an eQTL, one representative SNP among them was chosen at random. Paired-end RNA-Seq libraries for 53 rat eyes (one eye per rat) were aligned to the Rnor_6.0 genome using Spliced Transcripts Alignment to a Reference (STAR). The RNA-seq samples were tested for mismatches with their genotypes by inferring genotypes from RNA-seq reads and comparing them to DNA genotypes. We compared the RNA-inferred genotype from each rat to the DNA genotype of all other rats and found that 11 of the mismatched RNA samples were a strong match to a different DNA genotype, none of which already had a match, and could be recovered simply by relabeling the RNA samples, while the remaining two RNA samples had no high-similarity match in the DNA genotypes. Using these corrected RNA-seq/genotype pairs and removing the two remaining mismatches, we continued with 51 rat eye samples. The per-gene significance thresholds were computed by tensorQTL from data permutations, and false discovery rate (FDR) testing was performed across all genes using a q-value cutoff of 0.05. We also ran tensorQTL in cis nominal mode with larger cis-window sizes for genes of interest to obtain nominal p-values for all SNPs in the plotted regions. Log allelic fold change (aFC) of the eQTL used as a measure of effect size.

LABEL:

cis-eQTL related to IOP in HS outbred rats_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

712

DATE ADDED:

2024-12-10

DATE UPDATED:

2025-07-02

SPECIES:

AUTHORS:

Samuel Fowler, Tengfei Wang, Daniel Munro, Aman Kumar, Apurva S Chitre, T J Hollingsworth, Angel Garcia Martinez, Celine L St Pierre, Hannah Bimschleger, Jianjun Gao, Riyan Cheng, Pejman Mohammadi, Hao Chen, Abraham A Palmer, Oksana Polesskaya, Monica M Jablonski 

TITLE:

Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats

JOURNAL:

Frontiers in Genetics Jan 2023, Vol 13, pp.

ABSTRACT:

Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP is a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the genetic basis of IOP may lead to a better understanding of the molecular mechanisms of POAG. The goal of this study was to identify genetic loci involved in regulating IOP using outbred heterogeneous stock (HS) rats. HS rats are a multigenerational outbred population derived from eight inbred strains that have been fully sequenced. This population is ideal for a genome-wide association study (GWAS) owing to the accumulated recombinations among well-defined haplotypes, the relatively high allele frequencies, the accessibility to a large collection of tissue samples, and the large allelic effect size compared to human studies. Both male and female HS rats (N = 1,812) were used in the study. Genotyping-by-sequencing was used to obtain ∼3.5 million single nucleotide polymorphisms (SNP) from each individual. SNP heritability for IOP in HS rats was 0.32, which agrees with other studies. We performed a GWAS for the IOP phenotype using a linear mixed model and used permutation to determine a genome-wide significance threshold. We identified three genome-wide significant loci for IOP on chromosomes 1, 5, and 16. Next, we sequenced the mRNA of 51 whole eye samples to find cis-eQTLs to aid in identification of candidate genes. We report 5 candidate genes within those loci: Tyr, Ctsc, Plekhf2, Ndufaf6 and Angpt2. Tyr, Ndufaf6 and Angpt2 genes have been previously implicated by human GWAS of IOP-related conditions. Ctsc and Plekhf2 genes represent novel findings that may provide new insight into the molecular basis of IOP. This study highlights the efficacy of HS rats for investigating the genetics of elevated IOP and identifying potential candidate genes for future functional testing. PUBMED: 36793389
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Annotation Information

No sequence read archive data associated with this GeneSet.


Gene Frequency (D005787)
Alleles (D000483)
Pressure (D011312)
Genetics (D005823)
Chromosomes (D002875)
Genome-Wide Association Study (D055106)
Recombination, Genetic (D011995)
RNA, Messenger (D012333)
Insemination, Artificial, Heterologous (D007316)
Risk Factors (D012307)
Intraocular Pressure (D007429)
Genotype (D005838)
Phenotype (D010641)
Genetic Loci (D056426)
Tissues (D014024)
Nucleotides (D009711)
Glaucoma (D005901)
Glaucoma, Open-Angle (D005902)
Haplotypes (D006239)
Polymorphism, Single Nucleotide (D020641)
Association (D001244)
Alignment construction (EDAM_operation:2928)
Nucleic acid features (SNP) (EDAM_data:2092)
Genotype and phenotype (EDAM_topic:0625)
deoxyribonucleic acid (CHEBI:16991)
L-tyrosine residue (CHEBI:46858)
maleate(2-) (CHEBI:30780)
L-tyrosine (CHEBI:17895)
nucleotide (CHEBI:36976)
ribonucleic acid (CHEBI:33697)
messenger RNA (CHEBI:33699)
propyzamide (CHEBI:34935)
primary open angle glaucoma (DOID:1070)
glaucoma (DOID:1686)
open-angle glaucoma (DOID:1067)
DNA shearing (EFO:0004189)
phenotype (EFO:0000651)
risk factor (EFO:0003919)
transcription profiling by high throughput sequencing (EFO:0002770)
genotyping (EFO:0000750)
obsolete_eye structure (EFO:0000827)
open-angle glaucoma (EFO:0004190)
RNA-seq assay (MMO:0000659)
intraocular pressure (VT:0005257)
camera-type eye (UBERON:0000019)
central sulcus of insula (UBERON:0035925)
eyeball of camera-type eye (UBERON:0010230)
male organism (UBERON:0003101)
female organism (UBERON:0003100)

Gene List • 712 Genes

Genes in threshold: 712

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