Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans

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Wallis, Natalie J ORCID: 0000-0001-9543-3711, Mcclellan, Alyce, Morseburg, Alexander, Kentistou, Katherine A, Jamaluddin, Aqfan, Dowsett, Georgina KC, Schofield, Ellen, Morros-Nuevo, Anna, Saeed, Sadia, Lam, Brian YH et al (show 22 more authors) , Sumanasekera, Natasha T, Chan, Justine, Kumar, Sambhavi S, Zhang, Rey M, Wainwright, Jodie F, Dittmann, Marie, Lakatos, Gabriella, Rainbow, Kara, Withers, David, Bounds, Rebecca, Ma, Marcella, German, Alexander J ORCID: 0000-0002-3017-7988, Ladlow, Jane, Sargan, David, Froguel, Philippe, Farooqi, I Sadaf, Ong, Ken K, Yeo, Giles SH, Tadross, John A, Perry, John RB, Gorvin, Caroline M and Raffan, Eleanor (2025) Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans SCIENCE, 387 (6741). eads2145-. ISSN 0036-8075, 1095-9203

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Abstract

Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score—a measure of obesity—in 241 Labrador retrievers. Using a cross-species approach, we showed that canine obesity genes are also associated with rare and common forms of obesity in humans. The lead canine association was within the gene DENN domain containing 1B (DENND1B). Each copy of the alternate allele was associated with ~7.5% greater body fat. We demonstrate a role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified obesity genes and mechanisms relevant to both dogs and humans.

Item Type:	Article
Uncontrolled Keywords:	Adipose Tissue, Animals, Dogs, Humans, Obesity, Dog Diseases, Guanine Nucleotide Exchange Factors, Receptor, Melanocortin, Type 4, Signal Transduction, Polymorphism, Single Nucleotide, Alleles, Genome, Female, Male, Death Domain Receptor Signaling Adaptor Proteins, Genome-Wide Association Study
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	14 Mar 2025 08:12
Last Modified:	23 May 2026 09:53
DOI:	10.1126/science.ads2145
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3190786
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