Sequencing of 640,000 exomes identifies <i>GPR75</i> variants associated with protection from obesity
Parsa Akbari, Ankit Gilani, Olukayode Sosina, Jack A. Kosmicki, Lori Khrimian, Yi‐Ya Fang, Trikaldarshi Persaud, Víctor Garcia, Dylan Sun, Alexander Li, Joelle Mbatchou, Adam E. Locke, Christian Benner, Niek Verweij, Nan Lin, Sakib Hossain, Kevin Agostinucci, Jonathan V. Pascale, Ercument Dirice, Michael E. Dunn, William E. Kraus, Svati H. Shah, Yii‐Der I. Chen, Jerome I. Rotter, Daniel J. Rader, Olle Melander, Christopher D. Still, Tooraj Mirshahi, David J. Carey, Jaime Berúmen, Pablo Kuri‐Morales, Jesús Alegre-Díaz, Jason Torres, Jonathan Emberson, Rory Collins, Suganthi Balasubramanian, Alicia Hawes, Marcus Herbert Jones, Brian Zambrowicz, Andrew Murphy, Charles Paulding, Giovanni Coppola, John D. Overton, Jeffrey G. Reid, Alan R. Shuldiner, Michael Cantor, Hyun Min Kang, Gonçalo R. Abecasis, Katia Karalis, Aris N. Economides, Jonathan Marchini, George D. Yancopoulos, Mark W. Sleeman, Judith Y. Altarejos, Giusy Della Gatta, Roberto Tapia-Conyer, Michal L. Schwartzman, Aris Baras, Manuel A. R. Ferreira, Luca A. Lotta
Abstract
How genes affect human obesity Obesity is linked to many human diseases, including diabetes, cancer, and heart disease. There is thus great interest in understanding how genes predispose individuals to, or protect individuals from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI. Deletion of this gene in mice resulted in a resistance to weight gain, suggesting that this gene provides an avenue of study for the prevention or treatment of obesity. Science , abf8683, this issue p. eabf8683 ; see also abh3556, p. 30