TY - JOUR
T1 - Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans
AU - Wallis, Natalie J.
AU - McClellan, Alyce
AU - Mörseburg, Alexander
AU - Kentistou, Katherine A.
AU - Jamaluddin, Aqfan
AU - Dowsett, Georgina K. C.
AU - Schofield, Ellen
AU - Morros-Nuevo, Anna
AU - Saeed, Sadia
AU - Lam, Brian Y. H.
AU - Sumanasekera, Natasha T.
AU - Chan, Justine
AU - Kumar, Sambhavi S.
AU - Zhang, Rey M.
AU - Wainwright, Jodie F.
AU - Dittmann, Marie
AU - Lakatos, Gabriella
AU - Rainbow, Kara
AU - Withers, David
AU - Bounds, Rebecca
AU - Ma, Marcella
AU - German, Alexander J.
AU - Ladlow, Jane
AU - Sargan, David
AU - Froguel, Philippe
AU - Farooqi, I. Sadaf
AU - Ong, Ken K.
AU - Yeo, Giles S. H.
AU - Tadross, John A.
AU - Perry, John R. B.
AU - Gorvin, Caroline M.
AU - Raffan, Eleanor
N1 - © 2025 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1126/science.ads2145
PY - 2025/3/6
Y1 - 2025/3/6
N2 - 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 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.
AB - 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 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.
U2 - 10.1126/science.ads2145
DO - 10.1126/science.ads2145
M3 - Article
SN - 0036-8075
SP - 1
EP - 22
JO - Science
JF - Science
M1 - ads2145
ER -