Presenter Jade Scardham
Authors Jade Scardham¹, Alyce McClellan¹, Michelle Daya², Michael Denyer², Rebecca Chodroff Foran², Oliver Forman², Eleanor Raffan¹
Affiliations ¹University of Cambridge, Department of Physiology, Development and Neuroscience ²Wisdom Panel™, MARS Petcare Science & Diagnostics
Presentation Type Poster
Abstract
The melanocortin-4 receptor (MC4R) regulates appetite and energy homeostasis across species. Using genotype and veterinary phenotype data from a Wisdom Panel™ cohort of more than 700,000 genotyped dogs, we performed genome-wide association analyses of body condition score (BCS). Linear mixed models controlling for sex, neuter status, age, and population structure identified a highly significant association between BCS and the T allele at CanFam4 chr1:16,215,057 (β = +0.0338 ± 0.0018; p = 4.8 × 10⁻⁸⁰), corresponding to MC4R p.V213F (c.G637T, rs852614811). Effects were directionally concordant across multiple breeds (β ≈ +0.03–0.15) and slightly stronger in neutered than entire dogs.
In-vitro characterisation indicates partial loss-of-function for p.V213F, driven by reduced β-arrestin recruitment, a modest reduction in cAMP Emax, and lower surface expression, consistent with an obesity-increasing allele. Despite its small individual effect, the variant’s population-level significance highlights the value of large-scale canine cohorts for quantifying subtle genetic contributions to adiposity. This work demonstrates how integrating direct-to-consumer genotypes with electronic health phenotypes refines effect estimates at biologically validated loci.
Acknowledgments: We are grateful to the Banfield clinicians whose detailed and consistent medical records made this research possible, and to the Mars data and curation teams supporting the Wisdom Panel™ dataset. We thank the many dog owners who contributed samples and phenotypic information for research use.