Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

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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
Funding Information
  • National Institutes of Health (HL034300)
  • National Institutes of Health (HL139793)
  • National Institutes of Health (HL139793-1S)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK063491)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK063491)
  • National Center for Advancing Translational Sciences (UL1TR001881)
  • Regeneron Pharmaceuticals
  • Wellcome
  • Ministry of Health Mexico
  • Medical Research Council
  • British Heart Foundation
  • Cancer Research UK
  • Secretaría de Ciencia, Humanidades, Tecnología e Innovación
  • Nuffield Department of Population Health, University of Oxford
  • National Center for Advancing Translational Sciences (UL1TR001881)

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