Genome-wide association studies of inflammatory bowel disease in German shepherd dogs

Canine Inflammatory Bowel Disease (IBD) is considered a multifactorial disease caused by complex interactions between the intestinal immune system, intestinal microbiota and environmental factors in genetically susceptible individuals. Although IBD can affect any breed, German shepherd dogs (GSD) in the UK are at increased risk of developing the disease. Based on previous evidence, the aim of the present study was to identify single nucleotide polymorphisms (SNPs), which may confer genetic susceptibility or resistance to IBD using a genome-wide association study (GWAS). Genomic DNA was extracted from EDTA blood or saliva samples of 96 cases and 98 controls. Genotyping of cases and controls was performed on the Canine Illumina HD SNP array and data generated was analyzed using PLINK. Several SNPs and regions on chromosomes 7,9,11 and 13 were detected to be associated with IBD using different SNP-by-SNP association methods and FST windows approach. Searching one Mb up-and down-stream of the most significant SNPs, as identified by single SNP analysis as well as 200Kb before and after the start and the end position of the associated regions identified by FST windows approach, we identified 63 genes. Using a combination of pathways analysis and a list of genes that have been reported to be involved in human IBD, we identified 16 candidate genes potentially associated with IBD in GSD

Genome-wide association studies of inflammatory bowel disease in German shepherd dogs

Canine Inflammatory Bowel Disease (IBD) is considered a multifactorial disease caused by complex interactions between the intestinal immune system, intestinal microbiota and environmental factors in genetically susceptible individuals. Although IBD can affect any breed, German shepherd dogs (GSD) in the UK are at increased risk of developing the disease. Based on previous evidence, the aim of the present study was to identify single nucleotide polymorphisms (SNPs), which may confer genetic susceptibility or resistance to IBD using a genome-wide association study (GWAS). Genomic DNA was extracted from EDTA blood or saliva samples of 96 cases and 98 controls. Genotyping of cases and controls was performed on the Canine Illumina HD SNP array and data generated was analyzed using PLINK. Several SNPs and regions on chromosomes 7,9,11 and 13 were detected to be associated with IBD using different SNP-by-SNP association methods and FST windows approach. Searching one Mb up-and down-stream of the most significant SNPs, as identified by single SNP analysis as well as 200Kb before and after the start and the end position of the associated regions identified by FST windows approach, we identified 63 genes. Using a combination of pathways analysis and a list of genes that have been reported to be involved in human IBD, we identified 16 candidate genes potentially associated with IBD in GSD.This article is published as Peiravan A, Bertolini F, Rothschild MF, Simpson KW, Jergens AE, Allenspach K, et al. (2018) Genome-wide association studies of inflammatory bowel disease in German shepherd dogs. PLoS ONE 13(7): e0200685. doi: 10.1371/journal.pone.0200685.</p

Single F_ST approach result.

<p>SNPs with the highest F_ST value that overlap the basic case/control association test and logistic association are within red circles.</p

Scatter plot for the first 2 dimensions.

<p>The x-axis is principal component 1 and y-axis is principal component 2. Green: case, Blue: control.</p

Enricher results.

<p>Genes found to be enriched in biological processes and/or molecular components that are associated or directly/indirectly involved with human IBD.</p

The most significant SNPs found by basic case/control association analysis.

<p>The most significant SNPs found by basic case/control association analysis.</p

Genome-wide association studies of inflammatory bowel disease in German shepherd dogs - Fig 2

<p><b>Admixture plot of the case-control dataset (showed on the right) using the K with the lowest cross-validation error (showed on the left)</b>.</p

Regions on chromosome 7 and 13, found by F_ST windows approach.

<p>Regions on chromosome 7 and 13, found by F_ST windows approach.</p