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

Akbari, Parsa (author)
Regeneron Pharmaceuticals, Inc.
Gilani, Ankit (author)
New York Medical College
Sosina, Olukayode (author)
Regeneron Pharmaceuticals, Inc.
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Kosmicki, Jack A. (author)
Regeneron Pharmaceuticals, Inc.
Khrimian, Lori (author)
Regeneron Pharmaceuticals, Inc.
Fang, Yi Ya (author)
Regeneron Pharmaceuticals, Inc.
Persaud, Trikaldarshi (author)
Regeneron Pharmaceuticals, Inc.
Garcia, Victor (author)
New York Medical College
Sun, Dylan (author)
Regeneron Pharmaceuticals, Inc.
Li, Alexander (author)
Regeneron Pharmaceuticals, Inc.
Mbatchou, Joelle (author)
Regeneron Pharmaceuticals, Inc.
Locke, Adam E. (author)
Regeneron Pharmaceuticals, Inc.
Benner, Christian (author)
Regeneron Pharmaceuticals, Inc.
Verweij, Niek (author)
Regeneron Pharmaceuticals, Inc.
Lin, Nan (author)
Regeneron Pharmaceuticals, Inc.
Hossain, Sakib (author)
New York Medical College
Agostinucci, Kevin (author)
New York Medical College
Pascale, Jonathan V. (author)
New York Medical College
Dirice, Ercument (author)
New York Medical College
Dunn, Michael (author)
Regeneron Pharmaceuticals, Inc.
Kraus, William E. (author)
Duke University Medical Center
Shah, Svati H. (author)
Duke University Medical Center
Chen, Yii Der I. (author)
University of California, Los Angeles
Rotter, Jerome I. (author)
University of California, Los Angeles
Rader, Daniel J. (author)
University of Pennsylvania
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
Still, Christopher D. (author)
Geisinger Health System
Mirshahi, Tooraj (author)
Geisinger Health System
Carey, David J. (author)
Geisinger Health System
Berumen-Campos, Jaime (author)
National Autonomous University of Mexico
Kuri-Morales, Pablo (author)
National Autonomous University of Mexico
Alegre-Díaz, Jesus (author)
National Autonomous University of Mexico
Torres, Jason M. (author)
University of Oxford
Emberson, Jonathan R. (author)
University of Oxford
Collins, Rory (author)
University of Oxford
Balasubramanian, Suganthi (author)
Regeneron Pharmaceuticals, Inc.
Hawes, Alicia (author)
Regeneron Pharmaceuticals, Inc.
Jones, Marcus (author)
Regeneron Pharmaceuticals, Inc.
Zambrowicz, Brian (author)
Regeneron Pharmaceuticals, Inc.
Murphy, Andrew J. (author)
Regeneron Pharmaceuticals, Inc.
Paulding, Charles (author)
Regeneron Pharmaceuticals, Inc.
Coppola, Giovanni (author)
Regeneron Pharmaceuticals, Inc.
Overton, John D. (author)
Regeneron Pharmaceuticals, Inc.
Reid, Jeffrey G. (author)
Regeneron Pharmaceuticals, Inc.
Shuldiner, Alan R. (author)
Regeneron Pharmaceuticals, Inc.
Cantor, Michael (author)
Regeneron Pharmaceuticals, Inc.
Kang, Hyun M. (author)
Regeneron Pharmaceuticals, Inc.
Abecasis, Goncalo R. (author)
Regeneron Pharmaceuticals, Inc.
Karalis, Katia (author)
Regeneron Pharmaceuticals, Inc.
Economides, Aris N. (author)
Regeneron Pharmaceuticals, Inc.
Marchini, Jonathan (author)
Regeneron Pharmaceuticals, Inc.
Yancopoulos, George D (author)
Regeneron Pharmaceuticals, Inc.
Sleeman, Mark W. (author)
Regeneron Pharmaceuticals, Inc.
Altarejos, Judith (author)
Regeneron Pharmaceuticals, Inc.
Gatta, Giusy Della (author)
Regeneron Pharmaceuticals, Inc.
Tapia-Conyer, Roberto (author)
National Autonomous University of Mexico
Schwartzman, Michal L. (author)
New York Medical College
Baras, Aris (author)
Regeneron Pharmaceuticals, Inc.
Ferreira, Manuel A. R. (author)
Regeneron Pharmaceuticals, Inc.
Lotta, Luca A. (author)
Regeneron Pharmaceuticals, Inc.
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Regeneron Pharmaceuticals, Inc New York Medical College (creator_code:org_t)
 
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American Association for the Advancement of Science (AAAS), 2021
2021
English.
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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art (subject category)
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