@article {9526,
	title = {Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.},
	journal = {Nat Genet},
	volume = {50},
	year = {2018},
	month = {2018 Jan},
	pages = {26-41},
	abstract = {<p>Genome-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, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5\%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed~to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01\%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI~confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.</p>},
	issn = {1546-1718},
	doi = {10.1038/s41588-017-0011-x},
	author = {Turcot, Val{\'e}rie and Lu, Yingchang and Highland, Heather M and Schurmann, Claudia and Justice, Anne E and Fine, Rebecca S and Bradfield, Jonathan P and T{\~o}nu Esko and Giri, Ayush and Graff, Mariaelisa and Guo, Xiuqing and Hendricks, Audrey E and Karaderi, Tugce and Lempradl, Adelheid and Locke, Adam E and Mahajan, Anubha and Marouli, Eirini and Sivapalaratnam, Suthesh and Young, Kristin L and Alfred, Tamuno and Feitosa, Mary F and Masca, Nicholas G D and Alisa Manning and Medina-Gomez, Carolina and Mudgal, Poorva and Ng, Maggie C Y and Reiner, Alex P and Vedantam, Sailaja and Willems, Sara M and Thomas W Winkler and Gon{\c c}alo R Abecasis and Aben, Katja K and Alam, Dewan S and Alharthi, Sameer E and Matthew A. Allison and Amouyel, Philippe and Asselbergs, Folkert W and Auer, Paul L and Balkau, Beverley and Bang, Lia E and Barroso, In{\^e}s and Bastarache, Lisa and Benn, Marianne and Bergmann, Sven and Bielak, Lawrence F and Bl{\"u}her, Matthias and Boehnke, Michael and Boeing, Heiner and Boerwinkle, Eric and B{\"o}ger, Carsten A and Bork-Jensen, Jette and Bots, Michiel L and Erwin P Bottinger and Bowden, Donald W and Brandslund, Ivan and Breen, Gerome and Brilliant, Murray H and Broer, Linda and Brumat, Marco and Burt, Amber A and Adam S Butterworth and Campbell, Peter T and Cappellani, Stefania and Carey, David J and Catamo, Eulalia and Caulfield, Mark J and Chambers, John C and Daniel I Chasman and Yii-Der I Chen and Chowdhury, Rajiv and Cramer Christensen and Chu, Audrey Y and Cocca, Massimiliano and Collins, Francis S and Cook, James P and Corley, Janie and Jordi Corominas Galbany and Cox, Amanda J and Crosslin, David S and Cuellar-Partida, Gabriel and D{\textquoteright}Eustacchio, Angela and Danesh, John and Gail Davies and Bakker, Paul I W and Groot, Mark C H and Mutsert, Ren{\'e}e and Ian J Deary and George Dedoussis and Ellen W Demerath and Heijer, Martin and Anneke I den Hollander and Hester M den Ruijter and Joe G Dennis and Denny, Josh C and Angelantonio, Emanuele and Drenos, Fotios and Du, Mengmeng and Dub{\'e}, Marie-Pierre and Dunning, Alison M and Easton, Douglas F and Edwards, Todd L and Ellinghaus, David and Ellinor, Patrick T and Elliott, Paul and Evangelou, Evangelos and Farmaki, Aliki-Eleni and Farooqi, I Sadaf and Jessica Faul and Fauser, Sascha and Feng, Shuang and Ferrannini, Ele and Ferri{\`e}res, Jean and Florez, Jose C and Ford, Ian and Myriam Fornage and Franco, Oscar H and Franke, Andre and Franks, Paul W and Friedrich, Nele and Frikke-Schmidt, Ruth and Galesloot, Tessel E and Gan, Wei and Gandin, Ilaria and Paolo P. Gasparini and Gibson, Jane and Giedraitis, Vilmantas and Gjesing, Anette P and Gordon-Larsen, Penny and Gorski, Mathias and Hans-J{\"o}rgen Grabe and Grant, Struan F A and Grarup, Niels and Griffiths, Helen L and Grove, Megan L and Gudnason, Vilmundur and Gustafsson, Stefan and Jeffrey Haessler and Hakonarson, Hakon and Anke R Hammerschlag and Hansen, Torben and Tamara B Harris and Andrew T Hattersley and Have, Christian T and Caroline Hayward and He, Liang and Heard-Costa, Nancy L and Andrew C Heath and Iris M Heid and Helgeland, {\O}yvind and Hernesniemi, Jussi and Hewitt, Alex W and Oddgeir L Holmen and Hovingh, G Kees and Howson, Joanna M M and Hu, Yao and Huang, Paul L and Huffman, Jennifer E and Mohammed Arfan Ikram and Ingelsson, Erik and Jackson, Anne U and Jansson, Jan-H{\r a}kan and Jarvik, Gail P and Jensen, Gorm B and Jia, Yucheng and Johansson, Stefan and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Jukema, J Wouter and Kahali, Bratati and Kahn, Ren{\'e} S and K{\"a}h{\"o}nen, Mika and Kamstrup, Pia R and Kanoni, Stavroula and Kaprio, Jaakko and Karaleftheri, Maria and Sharon L R Kardia and Karpe, Fredrik and Kathiresan, Sekar and Kee, Frank and Lambertus A Kiemeney and Eric S Kim and Kitajima, Hidetoshi and Komulainen, Pirjo and Kooner, Jaspal S and Charles Kooperberg and Korhonen, Tellervo and Kovacs, Peter and Kuivaniemi, Helena and Kutalik, Zolt{\'a}n and Kuulasmaa, Kari and Kuusisto, Johanna and Laakso, Markku and Lakka, Timo A and Lamparter, David and Lange, Ethan M and Leslie A Lange and Langenberg, Claudia and Eric B Larson and Lee, Nanette R and Lehtim{\"a}ki, Terho and Lewis, Cora E and Li, Huaixing and Li, Jin and Li-Gao, Ruifang and Lin, Honghuang and Lin, Keng-Hung and Lin, Li-An and Lin, Xu and Lars Lind and Lindstr{\"o}m, Jaana and Linneberg, Allan and Liu, Ching-Ti and Liu, Dajiang J and Yongmei Liu and Ken Sin Lo and Lophatananon, Artitaya and Lotery, Andrew J and Loukola, Anu and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Lyytik{\"a}inen, Leo-Pekka and M{\"a}nnist{\"o}, Satu and Marenne, Ga{\"e}lle and Mazul, Angela L and McCarthy, Mark I and McKean-Cowdin, Roberta and Sarah E Medland and Meidtner, Karina and Lili Milani and Mistry, Vanisha and Mitchell, Paul and Mohlke, Karen L and Moilanen, Leena and Moitry, Marie and Grant W Montgomery and Dennis O Mook-Kanamori and Moore, Carmel and Mori, Trevor A and Morris, Andrew D and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Michael A Nalls and Narisu, Narisu and Nelson, Christopher P and Neville, Matt and Sune Fallgaard Nielsen and Nikus, Kjell and Nj{\o}lstad, P{\r a}l R and B{\o}rge G Nordestgaard and Nyholt, Dale R and Jeff O{\textquoteright}Connell and O{\textquoteright}Donoghue, Michelle L and Ophoff, Roel A and Owen, Katharine R and Packard, Chris J and Padmanabhan, Sandosh and Palmer, Colin N A and Palmer, Nicholette D and Pasterkamp, Gerard and Patel, Aniruddh P and Pattie, Alison and Pedersen, Oluf and Peissig, Peggy L and Peloso, Gina M and Pennell, Craig E and Markus Perola and Perry, James A and Perry, John R B and Pers, Tune H and Person, Thomas N and Peters, Annette and Petersen, Eva R B and Peyser, Patricia A and Pirie, Ailith and Polasek, Ozren and Tinca J Polderman and Puolijoki, Hannu and Olli T Raitakari and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Renstrom, Frida and Rheinberger, Myriam and Ridker, Paul M and Rioux, John D and Rivas, Manuel A and Roberts, David J and Neil R Robertson and Robino, Antonietta and Rolandsson, Olov and Rudan, Igor and Ruth, Katherine S and Saleheen, Danish and Veikko Salomaa and Nilesh J Samani and Sapkota, Yadav and Sattar, Naveed and Schoen, Robert E and Schreiner, Pamela J and Schulze, Matthias B and Scott, Robert A and Segura-Lepe, Marcelo P and Svati H Shah and Sheu, Wayne H-H and Sim, Xueling and Slater, Andrew J and Small, Kerrin S and Albert Vernon Smith and Southam, Lorraine and Timothy Spector and Elizabeth K Speliotes and John M Starr and Stefansson, Kari and Steinthorsdottir, Valgerdur and Kathleen E Stirrups and Strauch, Konstantin and Heather M Stringham and Stumvoll, Michael and Sun, Liang and Surendran, Praveen and Swift, Amy J and Tada, Hayato and Tansey, Katherine E and Tardif, Jean-Claude and Kent D Taylor and Teumer, Alexander and Thompson, Deborah J and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Thuesen, Betina H and T{\"o}njes, Anke and Tromp, Gerard and Trompet, Stella and Tsafantakis, Emmanouil and Tuomilehto, Jaakko and Tybjaerg-Hansen, Anne and Tyrer, Jonathan P and Uher, Rudolf and Andr{\'e} G Uitterlinden and Uusitupa, Matti and Laan, Sander W and Duijn, Cornelia M and Leeuwen, Nienke and van Setten, Jessica and Vanhala, Mauno and Varbo, Anette and Varga, Tibor V and Varma, Rohit and Digna R Velez Edwards and Vermeulen, Sita H and Veronesi, Giovanni and Vestergaard, Henrik and Vitart, Veronique and Vogt, Thomas F and V{\"o}lker, Uwe and Vuckovic, Dragana and Wagenknecht, Lynne E and Walker, Mark and Wallentin, Lars and Wang, Feijie and Wang, Carol A and Wang, Shuai and Wang, Yiqin and Erin B Ware and Wareham, Nicholas J and Warren, Helen R and Dawn M Waterworth and Wessel, Jennifer and White, Harvey D and Willer, Cristen J and Wilson, James G and Daniel Witte and Andrew R Wood and Wu, Ying and Yaghootkar, Hanieh and Yao, Jie and Yao, Pang and Laura M Yerges-Armstrong and Young, Robin and Zeggini, Eleftheria and Zhan, Xiaowei and Zhang, Weihua and Wei Zhao and Zhou, Wei and Krina T Zondervan and Rotter, Jerome I and Pospisilik, John A and Fernando Rivadeneira and Ingrid B Borecki and Deloukas, Panos and Timothy M Frayling and Lettre, Guillaume and Kari E North and Lindgren, Cecilia M and Joel N Hirschhron and Ruth J F Loos}
}
