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

Title: Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans
Authors: Wallis, NJ; McClellan, A; Mörseburg, A; Kentistou, KA; Jamaluddin, A; Dowsett, GKC; Schofield, E; Morros-Nuevo, A; Saeed, S; Lam, BYH; Sumanasekera, NT; Chan, J; Kumar, SS; Zhang, RM; Wainwright, JF; Dittmann, M; Lakatos, G; Rainbow, K; Withers, D; Bounds, R; Ma, M; German, AJ; Ladlow, J; Sargan, D; Froguel, P; Farooqi, IS; Ong, KK; Yeo, GSH; Tadross, JA; Perry, JRB; Gorvin, CM; Raffan, E
Publisher Information: American Association for the Advancement of Science (AAAS)
Publication Year: 2025
Collection: The University of Liverpool Repository
Description: 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.
Document Type: article in journal/newspaper
File Description: text
Language: English
ISSN: 0036-8075
Relation: https://livrepository.liverpool.ac.uk/3190786/1/Wallis_final_manuscript_with_figures_SHARE_main_supp%20%281%29.pdf; Collapse authors list. Wallis, NJ orcid:0000-0001-9543-3711 , McClellan, A, Mörseburg, A, Kentistou, KA, Jamaluddin, A, Dowsett, GKC, Schofield, E, Morros-Nuevo, A, Saeed, S, Lam, BYH et al (show 22 more authors) , Sumanasekera, NT, Chan, J, Kumar, SS, Zhang, RM, Wainwright, JF, Dittmann, M, Lakatos, G, Rainbow, K, Withers, D, Bounds, R, Ma, M, German, AJ orcid:0000-0002-3017-7988 , Ladlow, J, Sargan, D, Froguel, P, Farooqi, IS, Ong, KK, Yeo, GSH, Tadross, JA, Perry, JRB, Gorvin, CM and Raffan, E (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
DOI: 10.1126/science.ads2145
Availability: https://livrepository.liverpool.ac.uk/3190786/; https://doi.org/10.1126/science.ads2145; https://livrepository.liverpool.ac.uk/3190786/1/Wallis_final_manuscript_with_figures_SHARE_main_supp%20%281%29.pdf
Rights: cc_by_4
Accession Number: edsbas.BF013817
Database: BASE