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

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Fältnamn	Indikatorer	Metadata
000		06810naa a2201021 4500
001		oai:lup.lub.lu.se:3d414414-f96d-407d-ac3f-ba33611f898e
003		SwePub
008		210823s2021 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/3d414414-f96d-407d-ac3f-ba33611f898e2 URI
024	7	a https://doi.org/10.1126/science.abf86832 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Akbari, Parsau Regeneron Pharmaceuticals, Inc.4 aut
245	1 0	a Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
264	1	b American Association for the Advancement of Science (AAAS),c 2021
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
700	1	a Gilani, Ankitu New York Medical College4 aut
700	1	a Sosina, Olukayodeu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Kosmicki, Jack A.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Khrimian, Loriu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Fang, Yi Yau Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Persaud, Trikaldarshiu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Garcia, Victoru New York Medical College4 aut
700	1	a Sun, Dylanu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Li, Alexanderu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Mbatchou, Joelleu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Locke, Adam E.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Benner, Christianu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Verweij, Nieku Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Lin, Nanu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Hossain, Sakibu New York Medical College4 aut
700	1	a Agostinucci, Kevinu New York Medical College4 aut
700	1	a Pascale, Jonathan V.u New York Medical College4 aut
700	1	a Dirice, Ercumentu New York Medical College4 aut
700	1	a Dunn, Michaelu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Kraus, William E.u Duke University Medical Center4 aut
700	1	a Shah, Svati H.u Duke University Medical Center4 aut
700	1	a Chen, Yii Der I.u University of California, Los Angeles4 aut
700	1	a Rotter, Jerome I.u University of California, Los Angeles4 aut
700	1	a Rader, Daniel J.u University of Pennsylvania4 aut
700	1	a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)endo-ome
700	1	a Still, Christopher D.u Geisinger Health System4 aut
700	1	a Mirshahi, Tooraju Geisinger Health System4 aut
700	1	a Carey, David J.u Geisinger Health System4 aut
700	1	a Berumen-Campos, Jaimeu National Autonomous University of Mexico4 aut
700	1	a Kuri-Morales, Pablou National Autonomous University of Mexico4 aut
700	1	a Alegre-Díaz, Jesusu National Autonomous University of Mexico4 aut
700	1	a Torres, Jason M.u University of Oxford4 aut
700	1	a Emberson, Jonathan R.u University of Oxford4 aut
700	1	a Collins, Roryu University of Oxford4 aut
700	1	a Balasubramanian, Suganthiu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Hawes, Aliciau Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Jones, Marcusu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Zambrowicz, Brianu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Murphy, Andrew J.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Paulding, Charlesu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Coppola, Giovanniu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Overton, John D.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Reid, Jeffrey G.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Shuldiner, Alan R.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Cantor, Michaelu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Kang, Hyun M.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Abecasis, Goncalo R.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Karalis, Katiau Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Economides, Aris N.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Marchini, Jonathanu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Yancopoulos, George Du Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Sleeman, Mark W.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Altarejos, Judithu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Gatta, Giusy Dellau Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Tapia-Conyer, Robertou National Autonomous University of Mexico4 aut
700	1	a Schwartzman, Michal L.u New York Medical College4 aut
700	1	a Baras, Arisu Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Ferreira, Manuel A. R.u Regeneron Pharmaceuticals, Inc.4 aut
700	1	a Lotta, Luca A.u Regeneron Pharmaceuticals, Inc.4 aut
710	2	a Regeneron Pharmaceuticals, Inc.b New York Medical College4 org
710	2	a Regeneron Genetics Center
710	2	a DiscovEHR Collaboration
773	0	t Scienced : American Association for the Advancement of Science (AAAS)g 373:6550q 373:6550x 0036-8075x 1095-9203
856	4	u http://dx.doi.org/10.1126/science.abf8683y FULLTEXT
856	4	u https://www.ukbiobank.ac.uk/media/ezrderzw/applicant-mta.pdf
856	4 8	u https://lup.lub.lu.se/record/3d414414-f96d-407d-ac3f-ba33611f898e
856	4 8	u https://doi.org/10.1126/science.abf8683

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Av författaren/redakt...: Akbari, Parsa; Gilani, Ankit; Sosina, Olukayod ...; Kosmicki, Jack A ...; Khrimian, Lori; Fang, Yi Ya; visa fler...; Persaud, Trikald ...; Garcia, Victor; Sun, Dylan; Li, Alexander; Mbatchou, Joelle; Locke, Adam E.; Benner, Christia ...; Verweij, Niek; Lin, Nan; Hossain, Sakib; Agostinucci, Kev ...; Pascale, Jonatha ...; Dirice, Ercument; Dunn, Michael; Kraus, William E ...; Shah, Svati H.; Chen, Yii Der I.; Rotter, Jerome I ...; Rader, Daniel J.; Melander, Olle; Still, Christoph ...; Mirshahi, Tooraj; Carey, David J.; Berumen-Campos, ...; Kuri-Morales, Pa ...; Alegre-Díaz, Jes ...; Torres, Jason M.; Emberson, Jonath ...; Collins, Rory; Balasubramanian, ...; Hawes, Alicia; Jones, Marcus; Zambrowicz, Bria ...; Murphy, Andrew J ...; Paulding, Charle ...; Coppola, Giovann ...; Overton, John D.; Reid, Jeffrey G.; Shuldiner, Alan ...; Cantor, Michael; Kang, Hyun M.; Abecasis, Goncal ...; Karalis, Katia; Economides, Aris ...; Marchini, Jonath ...; Yancopoulos, Geo ...; Sleeman, Mark W.; Altarejos, Judit ...; Gatta, Giusy Del ...; Tapia-Conyer, Ro ...; Schwartzman, Mic ...; Baras, Aris; Ferreira, Manuel ...; Lotta, Luca A.; visa färre...

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