Genome wide association study of insect bite hypersensitivity in two populations of Icelandic horses

Equine Insect Bite Hypersensitivity (IBH) is a chronic, intensely pruritic, recurrent seasonal dermatitis. lt is caused by an allergie reaction to protein in the saliva of biting midges of the genus Culicoides and sometimes also ~he genus Simulium. IBH in harses is mediated by lgE type 1 and type IV hypersensitivity reactions. Clinical symptoms such as hair loss, thickening of skin and formation of skin lesions leads to discomfort and disfigurement that impairs the quality of life of the horse and economical loss for the horse owner. Severely affected harses
are sometimes euthanized. There are no cures or effective treatments for IBH till now, though preventive measures can ease the symptoms. IBH is a multifactorial disease that involves both environmental and genetic factors for development. The current worldwide prevalence ranges from 3% to 60%. Heritability for IBH has been estimated to be around 0.10 on the observable scale and 0.33 (sd=0.19) on the liability scale in Swedish born lcelandic harses, and to 0.24 (sd=0.06) for Dutch Sh etland breeding mares and 0.16 (sd=0.06) on the liability scale
for Friesian broodmares. Reducing prevalence through breeding is therefore possible, but traditional breeding would req uire extensive progeny testing, which is less efficient and not feasible in small breeds. lf genetic tests could be used this would improve the possibility to reduce IBH. With an aim to identify and quantify genomic regions associated with IBH, a genome wide association study was performed using lllumina Equine SOK SNP chip data for 209 Swedish born lcelandic harses, collected on a matched c~se control (104 cases and 105
controls) half sib design. The analysis was based on single marker effect using the GenABEL package in R. A genome-wide significant association was observed on chromosome 23. The odds ratio for IBH development of the unfavorable allele was 23.4 and had a frequency of 0.1 in cases compared to 0.004 in controls. However, this tentative association needs to be confirmed by re -genotyping the individuals included in GWAS as well as genotyping additional harses. Borderline associations were observed on chromosomes 3, 10, 17, 18 and 32. For
further confirmation association analysis using multi marker association model, based on a Bayesian variable selection method, will be performed. In addition, a combined GWAS will be performed on data of 146 lcelandic harses from the Netherlands and 209 lcelandic harses from Sweden using Bayesian methodology