Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity-Reference-Cited by-同舟云学术

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

Published:2021-07-02 Issue:6550 Volume:373 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Akbari Parsa¹^ORCID,Gilani Ankit²^ORCID,Sosina Olukayode¹^ORCID,Kosmicki Jack A.¹^ORCID,Khrimian Lori³^ORCID,Fang Yi-Ya³,Persaud Trikaldarshi¹^ORCID,Garcia Victor²^ORCID,Sun Dylan¹^ORCID,Li Alexander¹^ORCID,Mbatchou Joelle¹,Locke Adam E.¹^ORCID,Benner Christian¹,Verweij Niek¹^ORCID,Lin Nan¹,Hossain Sakib²,Agostinucci Kevin²,Pascale Jonathan V.²^ORCID,Dirice Ercument²^ORCID,Dunn Michael³,Kraus William E.⁴⁵^ORCID,Shah Svati H.⁶⁷,Chen Yii-Der I.⁸,Rotter Jerome I.⁸^ORCID,Rader Daniel J.⁹^ORCID,Melander Olle¹⁰¹¹,Still Christopher D.¹²^ORCID,Mirshahi Tooraj¹²^ORCID,Carey David J.¹²^ORCID,Berumen-Campos Jaime¹³^ORCID,Kuri-Morales Pablo¹³^ORCID,Alegre-Díaz Jesus¹³^ORCID,Torres Jason M.¹⁴^ORCID,Emberson Jonathan R.¹⁴^ORCID,Collins Rory¹⁴^ORCID,Balasubramanian Suganthi¹^ORCID,Hawes Alicia¹,Jones Marcus¹,Zambrowicz Brian³^ORCID,Murphy Andrew J.³^ORCID,Paulding Charles¹^ORCID,Coppola Giovanni¹^ORCID,Overton John D.¹^ORCID,Reid Jeffrey G.¹^ORCID,Shuldiner Alan R.¹^ORCID,Cantor Michael¹,Kang Hyun M.¹^ORCID,Abecasis Goncalo R.¹,Karalis Katia¹,Economides Aris N.¹³^ORCID,Marchini Jonathan¹^ORCID,Yancopoulos George D.³,Sleeman Mark W.³,Altarejos Judith³,Della Gatta Giusy¹^ORCID,Tapia-Conyer Roberto¹³^ORCID,Schwartzman Michal L.²,Baras Aris¹,Ferreira Manuel A. R.¹,Lotta Luca A.¹^ORCID, ,

Affiliation:

1. Regeneron Genetics Center, Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA.

2. Department of Pharmacology and Medicine, New York Medical College School of Medicine, Valhalla, NY 10595, USA.

3. Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA.

4. Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA.

5. Duke Center for Living, Duke University Medical Center, Durham, NC 27705, USA.

6. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

7. Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.

8. Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation, and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

9. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.

10. Department of Clinical Sciences Malmö, Lund University, 221 00 Malmö, Sweden.

11. Department of Emergency and Internal Medicine, Skåne University Hospital, 214 28, Malmö, Sweden.

12. Geisinger Obesity Institute, Geisinger Health System, Danville, PA 17882, USA.

13. Faculty of Medicine, National Autonomous University of Mexico, Copilco Universidad, Coyoacán, 4360 Ciudad de México, Mexico.

14. Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, England, UK.

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

Funder

National Institutes of Health

National Institute of Diabetes and Digestive and Kidney Diseases

National Center for Advancing Translational Sciences

Regeneron Pharmaceuticals

Wellcome

Ministry of Health Mexico

Medical Research Council

British Heart Foundation

Cancer Research UK

Consejo Nacional de Ciencia y Tecnología

Nuffield Department of Population Health, University of Oxford