# Genome-wide association study of idiopathic epilepsy in the Italian Spinone dog breed

## TL;DR

This study investigates the genetic basis of idiopathic epilepsy in the Italian Spinone dog breed using a genome-wide association approach.

## Contribution

The first genome-wide association study of idiopathic epilepsy in the Italian Spinone dog breed.

## Key findings

- Two genomic regions showed statistically significant association with idiopathic epilepsy in the GWAS meta-analysis.
- Findings were not replicated in the independent validation set.
- The study suggests that idiopathic epilepsy in the breed is not monogenic and highlights challenges in studying complex inherited diseases in small populations.

## Abstract

Idiopathic epilepsy (IE) has a high prevalence and a severe clinical course in the Italian Spinone breed of dog. A genome-wide association study meta-analysis of 52 cases and 51 controls was conducted to identify genomic regions that may be involved with the development of IE. Subsequent to the meta-analysis, a set of 175 controls and an independent validation set of 23 cases and 23 controls were genotyped for SNPs showing suggestive association with IE to find variants exhibiting evidence of replicable association and to test the predictiveness of SNPs for IE status when combined in a weighted risk score. Although two regions showed statistically significant association with IE in the GWAS meta-analysis, and additional regions with suggestive association were identified, the findings were not emulated in the validation set. This is the first GWAS of IE in the Italian Spinone, and the findings suggest that IE in the breed is not monogenic and demonstrates the challenges when investigating a multigenic or complex inherited disease in a numerically small domesticated animal population.