Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

Abstract

Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands.

Methods: Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case-control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions.

Results: The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules.

Conclusions: The genome-wide association study identified several genomic regions associated with insect bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on insect bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease insect bite hypersensitivity prevalence.

Figure 1

Multi-dimensional scaling plots of the genetic distance between animals in Shetland pony mares and Icelandic horses. Each point corresponds to one animal and indicates the distance between animals represented by the first two principal components (PC1 and PC2), based on the genomic kinship matrices.

Figure 2

Multi-dimensional scaling plot of the genetic distance between imported Icelandic horses and Icelandic horses born in Europe. Each point corresponds to one animal and indicates the distance between animals represented by the first two principal components (PC1 and PC2), based on the genomic kinship matrices.

Figure 3

Heat map comparing the percentage of genetic variance of insect bite hypersensitivity explained by each window in Shetland pony mares and Icelandic horses born in Europe. Non-overlapping 1 Mb windows are based on the physical order of consecutive SNP across the genome (ECA1 to X; build EquCab2.0); black bars represent windows explaining ≥ 0.14% of genetic variance and dashed black bars represent windows explaining between 0.12 and 0.14% of genetic variance; diminishing grey colour represents a decrease in genetic variance (< 0.12%) explained by windows.