GeneSet Information

Tier IV GS409689 • Genome-wide variant-gene markers associated with intraocular pressure (IOP) in heterogeneous stock (HS) outbred rats_pvalue

DESCRIPTION:

The aim of this study was to perform a GWAS in the heterogenous stock (HS) rat population to identify genomic regions that harbor variants responsible for the variation in intraocular pressure (IOP). We performed a GWAS for the IOP phenotype using a linear mixed model and used permutation to determine a genome-wide significance threshold. Both male and female HS rats (N=1,812) were used in the study. Genotyping-by-sequencing was used to obtain ~3.5M single nucleotide polymorphisms from each individual. We performed eQTL analysis using 51 rat eye samples. Log allelic fold change (aFC) of the eQTL used as a measure of effect size.

LABEL:

IOP gene variants HS outbred rats_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

14673

DATE ADDED:

2024-12-10

DATE UPDATED:

2024-12-10

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)
Population (D011153)
Alleles (D000483)
Pressure (D011312)
Forecasting (D005544)
Humans (D006801)
Genetics (D005823)
Genome (D016678)
Chromosomes (D002875)
Comprehension (D032882)
Eye (D005123)
Research Report (D058028)
Genome-Wide Association Study (D055106)
Recombination, Genetic (D011995)
RNA, Messenger (D012333)
Insemination, Artificial, Heterologous (D007316)
Risk Factors (D012307)
Risk (D012306)
Intraocular Pressure (D007429)
Weights and Measures (D014894)
Phenotype (D010641)
Genetic Loci (D056426)
Rats (D051381)
Tissues (D014024)
Nucleotides (D009711)
Glaucoma (D005901)
Glaucoma, Open-Angle (D005902)
Genes (D005796)
Haplotypes (D006239)
Lead (D007854)
Goals (D006040)
Collections (D020471)
Sprains and Strains (D013180)
Polymorphism, Single Nucleotide (D020641)
Association (D001244)
eye (MA:0000261)
Analysis (EDAM_operation:2945)
Genetics (EDAM_topic:3053)
Sequencing (EDAM_topic:3168)
Threshold (EDAM_data:2146)
Nucleic acid features (SNP) (EDAM_data:2092)
Report (EDAM_data:2048)
nucleotide (EDAM_format:1207)
Genotyping (EDAM_operation:3196)
Genotype and phenotype (EDAM_topic:0625)
Chromosomes (EDAM_topic:0624)
DNA (EDAM_topic:0654)
SNPs (EDAM_topic:2277)
lead atom (CHEBI:25016)
Carfentrazone-ethyl (CHEBI:3416)
L-tyrosine residue (CHEBI:46858)
maleate(2-) (CHEBI:30780)
tyrosine (CHEBI:18186)
L-tyrosine (CHEBI:17895)
nucleotide (CHEBI:36976)
messenger RNA (CHEBI:33699)
lead(0) (CHEBI:27889)
primary open angle glaucoma (DOID:1070)
glaucoma (DOID:1686)
open-angle glaucoma (DOID:1067)
individual (EFO:0000542)
outbred (EFO:0004430)
phenotype (EFO:0000651)
risk factor (EFO:0003919)
size (EFO:0001695)
genotyping (EFO:0000750)
obsolete_eye structure (EFO:0000827)
open-angle glaucoma (EFO:0004190)
genome (EFO:0004420)
inbred (EFO:0004429)
intraocular pressure (VT:0005257)
camera-type eye (UBERON:0000019)
central sulcus of insula (UBERON:0035925)
eyeball of camera-type eye (UBERON:0010230)
tissue (UBERON:0000479)
male organism (UBERON:0003101)
female organism (UBERON:0003100)
eye (UBERON:0000970)
tissue (MA:0003002)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

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