Over the first 3 years of this study, we have focused primarily on sample collection and running an initial set of genetics experiments. We collected samples mostly through PWD-related channels working directly with our collaborators in the PWDF/PWDCA. We also attended the PWD National Specialty in September 2021 and August 2022 to promote the study and collect samples, and we established a collaboration with Dr. Anita Oberbauer at UC Davis to share samples that she had already collected. To date, we have in hand 151 samples from affected PWDs and 319 samples from unaffected PWDs. Based upon relatedness, we have performed low-pass whole genome sequencing on 46 affected dogs and 55 unaffected dogs, and we have used data from these genotyping efforts to perform a genome-wide association study (GWAS). This initial study using traditional GWAS analysis approaches did not detect any major genetic differences between affected and unaffected PWDs. This is consistent with our thinking that the disease is genetically “complex.”
We then looked at the same data from 46 affected/55 unaffected dogs using two other analysis approaches which can identify subtler differences between cases and controls as well as regions of the genome that are under active selection in PWDs. These analyses highlighted several regions of the genome that could harbor genes important in the development of Addison’s disease in PWDs, and we are actively analyzing these genes at the moment.
We also performed an updated analysis of the variations in a set of genes called the major histocompatibility complex genes. These genes are very important in the immune system. We found one “version” of this gene set that continues to be associated with Addison’s disease in PWDs – which is consistent with what we found in the last progress report.
We look forward to ongoing fruitful collaborations with the PWDF and PWDCA on this work.