Wallis, NJ;
McClellan, A;
Mörseburg, A;
Kentistou, KA;
Jamaluddin, A;
Dowsett, GKC;
Schofield, E;
... Raffan, E; + view all
(2025)
Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans.
Science
, 387
(6741)
, Article eads2145. 10.1126/science.ads2145.
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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% 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.
| Type: | Article |
|---|---|
| Title: | Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/science.ads2145 |
| Publisher version: | https://doi.org/10.1126/science.ads2145 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Animals, Dogs, Female, Humans, Male, Adipose Tissue, Alleles, Dog Diseases, Genome-Wide Association Study, Obesity, Polymorphism, Single Nucleotide, Receptor, Melanocortin, Type 4, Signal Transduction, Genome, Guanine Nucleotide Exchange Factors, Death Domain Receptor Signaling Adaptor Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10209675 |
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