Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans
Year: 2025
Type: article
Abstract: Obesity is a far-reaching, heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed the first successful canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers, with a polygenic score replicated in 350 more. Using an innovative cross-species approach, we showed new canine obesity genes are also associated with rare and common forms of obesity in humans. The lead association in dogs was with rs24430444 within the gene DENN domain containing 1B (DENND1B). Each copy of the alternate allele was associated with ~7% greater body fat per allele. We demonstrate a novel role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified novel obesity genes and mechanisms relevant to both dogs and humans.
Source: Apollo (University of Cambridge)
DOI: 10.17863/cam.115968
Authors: Wallis, Natalie, McClellan, Alyce, Mörseburg, Alexander, Kentistou, Katherine, Jamaluddin, Aqfan, Dowsett, Georgina, Schofield, Ellen, Morros Nuevo, Anna, Saeed, Sadia, Lam, Brian, Sumanasakera, Natasha, Chan, Justine Tin Nok, Kumar, Sambhavi, Rey, Zhang, Wainwright, Jodie, Dittmann, Marie, Lakatos, Gabriella, Rainbow, Kara, Withers, David, Bounds, Rebecca, Ma, Marcella, German, Alexander, Ladlow, Jane, Sargan, David, Froguel, Phillipe, Farooqi, Sadaf, Ong, Ken, Yeo, Giles, Tadross, John, Perry, John, Gorvin, Caroline, Raffan, Eleanor
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1011367695, Mapping the neuronal functional architecture underlying appetite control in humans at the extremes of bodyweight, Obesity: Exploiting Genomes for Novel Insights, Mapping the human hypothalamic functional architecture underlying food intake control, Fundamental mechanisms controlling human energy homeostasis, Genetic Underpinnings of Canine Obesity
OpenAlex ID: W6925463042
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