Abstract
Dogs with idiopathic epilepsy (IE) have a lowered threshold for seizures, including
generalized tonic-clonic (GTC) and focal seizures (FS). In some breeds, like
Labrador Retrievers (LR), paroxysmal dyskinesia (PD) causes episodes which may
resemble FS. Despite the genetic susceptibility of IE in many breeds, the contributing
variants remain largely unknown. We aimed to identify the major loci and
common variants associated with the risk of IE and PD in dogs by performing
large-scale GWAS in two cohorts. The first cohort included 280 LR categorized
based on their diagnoses (IE vs PD) and episode types (GTC vs non-GTC) and
460 controls. The second multi-breed cohort included ~5,000 dogs with reported
seizures and 10,000 controls from > 100 breeds. Analyses in both cohorts revealed
a 27.8 kb risk haplotype overlapping ADAM23 on CFA 37. The risk haplotype was
associated with non-GTC seizures and PD in LR, but not with GTC seizures. WGS
analyses revealed two non-synonymous exonic variants in ADAM23 within the
same coding triplet in exon 12. Preliminary functional studies in cell cultures suggest
an effect of these variants on ADAM23 interaction with LGI1, previously implicated
in epilepsy. We also continue Bayesian analyses, which suggest additional
associated loci and candidate genes. This is the largest GWAS of canine epilepsy,
which will help us better understand the genetic background of the most common
neurological disease in dogs.
generalized tonic-clonic (GTC) and focal seizures (FS). In some breeds, like
Labrador Retrievers (LR), paroxysmal dyskinesia (PD) causes episodes which may
resemble FS. Despite the genetic susceptibility of IE in many breeds, the contributing
variants remain largely unknown. We aimed to identify the major loci and
common variants associated with the risk of IE and PD in dogs by performing
large-scale GWAS in two cohorts. The first cohort included 280 LR categorized
based on their diagnoses (IE vs PD) and episode types (GTC vs non-GTC) and
460 controls. The second multi-breed cohort included ~5,000 dogs with reported
seizures and 10,000 controls from > 100 breeds. Analyses in both cohorts revealed
a 27.8 kb risk haplotype overlapping ADAM23 on CFA 37. The risk haplotype was
associated with non-GTC seizures and PD in LR, but not with GTC seizures. WGS
analyses revealed two non-synonymous exonic variants in ADAM23 within the
same coding triplet in exon 12. Preliminary functional studies in cell cultures suggest
an effect of these variants on ADAM23 interaction with LGI1, previously implicated
in epilepsy. We also continue Bayesian analyses, which suggest additional
associated loci and candidate genes. This is the largest GWAS of canine epilepsy,
which will help us better understand the genetic background of the most common
neurological disease in dogs.
| Original language | English |
|---|---|
| Pages | 26 |
| Number of pages | 1 |
| Publication status | Published - 10 Jun 2024 |
| Event | ICCFGG 2024 - Helsinki, Finland Duration: 9 Jun 2024 → 12 Jun 2024 |
Conference
| Conference | ICCFGG 2024 |
|---|---|
| Country/Territory | Finland |
| City | Helsinki |
| Period | 9/06/24 → 12/06/24 |