Canine genome-wide association study identifies <i>DENND1B</i> as an obesity gene in dogs and humans
Natalie Wallis, Alyce McClellan, Alexander Mörseburg, Katherine A. Kentistou, Aqfan Jamaluddin, Georgina K.C. Dowsett, Ellen Schofield, Anna Morros‐Nuevo, Sadia Saeed, Brian Lam, Natasha T. Sumanasekera, J. Chan, Sambhavi S. Kumar, Rey M. Zhang, Jodie Wainwright, Marie T. Dittmann, Gabriella Lakatos, Kara Rainbow, David Withers, Rebecca Bounds, Marcella Ma, Alexander J. German, Jane 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
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.