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

作者：Natalie J. Wallis, Alyce McClellan, Alexander Mörseburg, Katherine A. Kentistou, Aqfan Jamaluddin, Georgina K.C. Dowsett, Ellen C. Schofield, Anna Morros-Nuevo, Sadia Saeed, Brian Y.H. Lam, Natasha T. Sumanasekera, Justine Tin Nok Chan, Sambhavi S. Kumar, Rey M. Zhang, Jodie F. Wainwright, Marie Theres Dittmann, Gabriella Lakatos, Kara Rainbow, David Withers, Rebecca Bounds, Marcella K.L. Ma, Alexander J. German, Jane F. Ladlow, David R. Sargan, Philippe Froguel, I. Sadaf Farooqi, Ken K. Ong, Giles S.H. Yeo, John A. Tadross, John R. B. Perry, Caroline M. Gorvin, Eleanor Raffan · 发表于：Science · 年份：2025 · DOI：10.1126/science.ads2145 · 被引用次数：17 · 研究领域：Diet and metabolism studies、Adipose Tissue and Metabolism、Epigenetics and DNA Methylation

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.