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dc.contributor.authorTurcot, Valérieen_US
dc.contributor.authorLu, Yingchangen_US
dc.contributor.authorHighland, Heather Men_US
dc.contributor.authorSchurmann, Claudiaen_US
dc.contributor.authorJustice, Anne Een_US
dc.contributor.authorFine, Rebecca Sen_US
dc.contributor.authorBradfield, Jonathan Pen_US
dc.contributor.authorEsko, Tõnuen_US
dc.contributor.authorGiri, Ayushen_US
dc.contributor.authorGraff, Mariaelisaen_US
dc.contributor.authorGuo, Xiuqingen_US
dc.contributor.authorHendricks, Audrey Een_US
dc.contributor.authorKaraderi, Tugceen_US
dc.contributor.authorLempradl, Adelheiden_US
dc.contributor.authorLocke, Adam Een_US
dc.contributor.authorMahajan, Anubhaen_US
dc.contributor.authorMarouli, Eirinien_US
dc.contributor.authorSivapalaratnam, Sutheshen_US
dc.contributor.authorYoung, Kristin Len_US
dc.contributor.authorAlfred, Tamunoen_US
dc.contributor.authorFeitosa, Mary Fen_US
dc.contributor.authorMasca, Nicholas GDen_US
dc.contributor.authorManning, Alisa Ken_US
dc.contributor.authorMedina-Gomez, Carolinaen_US
dc.contributor.authorMudgal, Poorvaen_US
dc.contributor.authorNg, Maggie CYen_US
dc.contributor.authorReiner, Alex Pen_US
dc.contributor.authorVedantam, Sailajaen_US
dc.contributor.authorWillems, Sara Men_US
dc.contributor.authorWinkler, Thomas Wen_US
dc.contributor.authorAbecasis, Goncaloen_US
dc.contributor.authorAben, Katja Ken_US
dc.contributor.authorAlam, Dewan Sen_US
dc.contributor.authorAlharthi, Sameer Een_US
dc.contributor.authorAllison, Matthewen_US
dc.contributor.authorAmouyel, Philippeen_US
dc.contributor.authorAsselbergs, Folkert Wen_US
dc.contributor.authorAuer, Paul Len_US
dc.contributor.authorBalkau, Beverleyen_US
dc.contributor.authorBang, Lia Een_US
dc.contributor.authorBarroso, Inêsen_US
dc.contributor.authorBastarache, Lisaen_US
dc.contributor.authorBenn, Marianneen_US
dc.contributor.authorBergmann, Svenen_US
dc.contributor.authorBielak, Lawrence Fen_US
dc.contributor.authorBlüher, Matthiasen_US
dc.contributor.authorBoehnke, Michaelen_US
dc.contributor.authorBoeing, Heineren_US
dc.contributor.authorBoerwinkle, Ericen_US
dc.contributor.authorBöger, Carsten Aen_US
dc.contributor.authorBork-Jensen, Jetteen_US
dc.contributor.authorBots, Michiel Len_US
dc.contributor.authorBottinger, Erwin Pen_US
dc.contributor.authorBowden, Donald Wen_US
dc.contributor.authorBrandslund, Ivanen_US
dc.contributor.authorBreen, Geromeen_US
dc.contributor.authorBrilliant, Murray Hen_US
dc.contributor.authorBroer, Lindaen_US
dc.contributor.authorBrumat, Marcoen_US
dc.contributor.authorBurt, Amber Aen_US
dc.contributor.authorButterworth, Adam Sen_US
dc.contributor.authorCampbell, Peter Ten_US
dc.contributor.authorCappellani, Stefaniaen_US
dc.contributor.authorCarey, David Jen_US
dc.contributor.authorCatamo, Eulaliaen_US
dc.contributor.authorCaulfield, Mark Jen_US
dc.contributor.authorChambers, John Cen_US
dc.contributor.authorChasman, Daniel Ien_US
dc.contributor.authorChen, Yii-Der Idaen_US
dc.contributor.authorChowdhury, Rajiven_US
dc.contributor.authorChristensen, Crameren_US
dc.contributor.authorChu, Audrey Yen_US
dc.contributor.authorCocca, Massimilianoen_US
dc.contributor.authorCollins, Francis Sen_US
dc.contributor.authorCook, James Pen_US
dc.contributor.authorCorley, Janieen_US
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dc.contributor.authorCox, Amanda Jen_US
dc.contributor.authorCrosslin, David Sen_US
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dc.contributor.authorD'Eustacchio, Angelaen_US
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dc.contributor.authorDedoussis, Georgeen_US
dc.contributor.authorDemerath, Ellen Wen_US
dc.contributor.authorden Heijer, Martinen_US
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dc.contributor.authorden Ruijter, Hester Men_US
dc.contributor.authorDennis, Joe Gen_US
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dc.contributor.authorDi Angelantonio, Emanueleen_US
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dc.contributor.authorEllinor, Patrick Ten_US
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dc.contributor.authorFaul, Jessica Den_US
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dc.contributor.authorFeng, Shuangen_US
dc.contributor.authorFerrannini, Eleen_US
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dc.contributor.authorFlorez, Jose Cen_US
dc.contributor.authorFord, Ianen_US
dc.contributor.authorFornage, Myriamen_US
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dc.contributor.authorFranke, Andreen_US
dc.contributor.authorFranks, Paul Wen_US
dc.contributor.authorFriedrich, Neleen_US
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dc.contributor.authorGasparini, Paoloen_US
dc.contributor.authorGibson, Janeen_US
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dc.contributor.authorGrarup, Nielsen_US
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dc.contributor.authorHarris, Tamara Ben_US
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dc.contributor.authorHe, Liangen_US
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dc.contributor.authorHernesniemi, Jussien_US
dc.contributor.authorHewitt, Alex Wen_US
dc.contributor.authorHolmen, Oddgeir Len_US
dc.contributor.authorHovingh, G Keesen_US
dc.contributor.authorHowson, Joanna MMen_US
dc.contributor.authorHu, Yaoen_US
dc.contributor.authorHuang, Paul Len_US
dc.contributor.authorHuffman, Jennifer Een_US
dc.contributor.authorIkram, M Arfanen_US
dc.contributor.authorIngelsson, Eriken_US
dc.contributor.authorJackson, Anne Uen_US
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dc.contributor.authorJarvik, Gail Pen_US
dc.contributor.authorJensen, Gorm Ben_US
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dc.contributor.authorJohansson, Stefanen_US
dc.contributor.authorJørgensen, Marit Een_US
dc.contributor.authorJørgensen, Torbenen_US
dc.contributor.authorJukema, J Wouteren_US
dc.contributor.authorKahali, Bratatien_US
dc.contributor.authorKahn, René Sen_US
dc.contributor.authorKähönen, Mikaen_US
dc.contributor.authorKamstrup, Pia Ren_US
dc.contributor.authorKanoni, Stavroulaen_US
dc.contributor.authorKaprio, Jaakkoen_US
dc.contributor.authorKaraleftheri, Mariaen_US
dc.contributor.authorKardia, Sharon LRen_US
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dc.contributor.authorKathiresan, Sekaren_US
dc.contributor.authorKee, Franken_US
dc.contributor.authorKiemeney, Lambertus Aen_US
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dc.contributor.authorKooner, Jaspal Sen_US
dc.contributor.authorKooperberg, Charlesen_US
dc.contributor.authorKorhonen, Tellervoen_US
dc.contributor.authorKovacs, Peteren_US
dc.contributor.authorKuivaniemi, Helenaen_US
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dc.contributor.authorKuulasmaa, Karien_US
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dc.contributor.authorLangenberg, Claudiaen_US
dc.contributor.authorLarson, Eric Ben_US
dc.contributor.authorLee, Nanette Ren_US
dc.contributor.authorLehtimäki, Terhoen_US
dc.contributor.authorLewis, Cora Een_US
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dc.contributor.authorLi, Jinen_US
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dc.contributor.authorLin, Keng-Hungen_US
dc.contributor.authorLin, Li-Anen_US
dc.contributor.authorLin, Xuen_US
dc.contributor.authorLind, Larsen_US
dc.contributor.authorLindström, Jaanaen_US
dc.contributor.authorLinneberg, Allanen_US
dc.contributor.authorLiu, Ching-Tien_US
dc.contributor.authorLiu, Dajiang Jen_US
dc.contributor.authorLiu, Yongmeien_US
dc.contributor.authorLo, Ken Sinen_US
dc.contributor.authorLophatananon, Artitayaen_US
dc.contributor.authorLotery, Andrew Jen_US
dc.contributor.authorLoukola, Anuen_US
dc.contributor.authorLuan, Jian'anen_US
dc.contributor.authorLubitz, Steven Aen_US
dc.contributor.authorLyytikäinen, Leo-Pekkaen_US
dc.contributor.authorMännistö, Satuen_US
dc.contributor.authorMarenne, Gaëlleen_US
dc.contributor.authorMazul, Angela Len_US
dc.contributor.authorMcCarthy, Mark Ien_US
dc.contributor.authorMcKean-Cowdin, Robertaen_US
dc.contributor.authorMedland, Sarah Een_US
dc.contributor.authorMeidtner, Karinaen_US
dc.contributor.authorMilani, Lilien_US
dc.contributor.authorMistry, Vanishaen_US
dc.contributor.authorMitchell, Paulen_US
dc.contributor.authorMohlke, Karen Len_US
dc.contributor.authorMoilanen, Leenaen_US
dc.contributor.authorMoitry, Marieen_US
dc.contributor.authorMontgomery, Grant Wen_US
dc.contributor.authorMook-Kanamori, Dennis Oen_US
dc.contributor.authorMoore, Carmelen_US
dc.contributor.authorMori, Trevor Aen_US
dc.contributor.authorMorris, Andrew Den_US
dc.contributor.authorMorris, Andrew Pen_US
dc.contributor.authorMüller-Nurasyid, Martinaen_US
dc.contributor.authorMunroe, Patricia Ben_US
dc.contributor.authorNalls, Mike Aen_US
dc.contributor.authorNarisu, Narisuen_US
dc.contributor.authorNelson, Christopher Pen_US
dc.contributor.authorNeville, Matten_US
dc.contributor.authorNielsen, Sune Fen_US
dc.contributor.authorNikus, Kjellen_US
dc.contributor.authorNjølstad, Pål Ren_US
dc.contributor.authorNordestgaard, Børge Gen_US
dc.contributor.authorNyholt, Dale Ren_US
dc.contributor.authorO'Connel, Jeffrey Ren_US
dc.contributor.authorO’Donoghue, Michelle L.en_US
dc.contributor.authorOlde Loohuis, Loes Men_US
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dc.contributor.authorPackard, Chris Jen_US
dc.contributor.authorPadmanabhan, Sandoshen_US
dc.contributor.authorPalmer, Colin NAen_US
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dc.contributor.authorPasterkamp, Gerarden_US
dc.contributor.authorPatel, Aniruddh Pen_US
dc.contributor.authorPattie, Alisonen_US
dc.contributor.authorPedersen, Olufen_US
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dc.contributor.authorUusitupa, Mattien_US
dc.contributor.authorvan der Laan, Sander Wen_US
dc.contributor.authorvan Duijn, Cornelia Men_US
dc.contributor.authorvan Leeuwen, Nienkeen_US
dc.contributor.authorvan Setten, Jessicaen_US
dc.contributor.authorVanhala, Maunoen_US
dc.contributor.authorVarbo, Anetteen_US
dc.contributor.authorVarga, Tibor Ven_US
dc.contributor.authorVarma, Rohiten_US
dc.contributor.authorVelez Edwards, Digna Ren_US
dc.contributor.authorVermeulen, Sita Hen_US
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dc.contributor.authorWitte, Daniel Ren_US
dc.contributor.authorWood, Andrew Ren_US
dc.contributor.authorWu, Yingen_US
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dc.contributor.authorYao, Jieen_US
dc.contributor.authorYao, Pangen_US
dc.contributor.authorYerges-Armstrong, Laura Men_US
dc.contributor.authorYoung, Robinen_US
dc.contributor.authorZeggini, Eleftheriaen_US
dc.contributor.authorZhan, Xiaoweien_US
dc.contributor.authorZhang, Weihuaen_US
dc.contributor.authorZhao, Jing Huaen_US
dc.contributor.authorZhao, Weien_US
dc.contributor.authorZhou, Weien_US
dc.contributor.authorZondervan, Krina Ten_US
dc.contributor.authorRotter, Jerome Ien_US
dc.contributor.authorPospisilik, John Aen_US
dc.contributor.authorRivadeneira, Fernandoen_US
dc.contributor.authorBorecki, Ingrid Ben_US
dc.contributor.authorDeloukas, Panosen_US
dc.contributor.authorFrayling, Timothy Men_US
dc.contributor.authorLettre, Guillaumeen_US
dc.contributor.authorNorth, Kari Een_US
dc.contributor.authorLindgren, Cecilia Men_US
dc.contributor.authorHirschhorn, Joel Nen_US
dc.contributor.authorLoos, Ruth JFen_US
dc.date.accessioned2018-07-25T14:24:32Z
dc.date.issued2018en_US
dc.identifier.citationTurcot, V., Y. Lu, H. M. Highland, C. Schurmann, A. E. Justice, R. S. Fine, J. P. Bradfield, et al. 2018. “Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity.” Nature genetics 50 (1): 26-41. doi:10.1038/s41588-017-0011-x. http://dx.doi.org/10.1038/s41588-017-0011-x.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:37298514
dc.description.abstractGenome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169) newly implicated in human obesity, two (MC4R, KSR2) previously observed in extreme obesity, and two variants in GIPR. Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/s41588-017-0011-xen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945951/pdf/en
dash.licenseLAAen_US
dc.titleProtein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesityen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature geneticsen
dash.depositing.authorFine, Rebecca Sen_US
dc.date.available2018-07-25T14:24:32Z
dc.identifier.doi10.1038/s41588-017-0011-x*
dash.authorsorderedfalse
dash.contributor.affiliatedFine, Rebecca
dash.contributor.affiliatedManning, Alisa
dash.contributor.affiliatedChasman, Daniel
dash.contributor.affiliatedFlorez, Jose
dash.contributor.affiliatedEllinor, Patrick
dash.contributor.affiliatedFranks, Paul
dash.contributor.affiliatedHuang, Paul
dash.contributor.affiliatedLubitz, Steven
dash.contributor.affiliatedPatel, Aniruddh
dash.contributor.affiliatedRidker, Paul
dash.contributor.affiliatedHirschhorn, Joel
dc.identifier.orcid0000-0003-1249-4522


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