Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
Akbari P., Gilani A., Sosina O., Kosmicki JA., Khrimian L., Fang Y-Y., Persaud T., Garcia V., Sun D., Li A., Mbatchou J., Locke AE., Benner C., Verweij N., Lin N., Hossain S., Agostinucci K., Pascale JV., Dirice E., Dunn M., Kraus WE., Shah SH., Chen Y-DI., Rotter JI., Rader DJ., Melander O., Still CD., Mirshahi T., Carey DJ., Berumen-Campos J., Kuri-Morales P., Alegre-Díaz J., Torres JM., Emberson JR., Collins R., Balasubramanian S., Hawes A., Jones M., Zambrowicz B., Murphy AJ., Paulding C., Coppola G., Overton JD., Reid JG., Shuldiner AR., Cantor M., Kang HM., Abecasis GR., Karalis K., Economides AN., Marchini J., Yancopoulos GD., Sleeman MW., Altarejos J., Della Gatta G., Tapia-Conyer R., Schwartzman ML., Baras A., Ferreira MAR., Lotta LA.
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