@article {8886,
	title = {Rare and low-frequency coding variants alter human adult height.},
	journal = {Nature},
	volume = {542},
	year = {2017},
	month = {2017 Feb 09},
	pages = {186-190},
	abstract = {<p>Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8\%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.</p>},
	issn = {1476-4687},
	doi = {10.1038/nature21039},
	author = {Marouli, Eirini and Graff, Mariaelisa and Medina-Gomez, Carolina and Ken Sin Lo and Andrew R Wood and Kjaer, Troels R and Fine, Rebecca S and Lu, Yingchang and Schurmann, Claudia and Highland, Heather M and R{\"u}eger, Sina and Thorleifsson, Gudmar and Justice, Anne E and Lamparter, David and Kathleen E Stirrups and Turcot, Val{\'e}rie and Young, Kristin L and Thomas W Winkler and T{\~o}nu Esko and Karaderi, Tugce and Locke, Adam E and Masca, Nicholas G D and Ng, Maggie C Y and Mudgal, Poorva and Rivas, Manuel A and Vedantam, Sailaja and Mahajan, Anubha and Guo, Xiuqing and Gon{\c c}alo R Abecasis and Aben, Katja K and Adair, Linda S and Alam, Dewan S and Albrecht, Eva and Allin, Kristine H and Matthew A. Allison and Amouyel, Philippe and Appel, Emil V and Arveiler, Dominique and Asselbergs, Folkert W and Auer, Paul L and Balkau, Beverley and Banas, Bernhard and Bang, Lia E and Benn, Marianne and Bergmann, Sven and Bielak, Lawrence F and Bl{\"u}her, Matthias and Boeing, Heiner and Boerwinkle, Eric and B{\"o}ger, Carsten A and Bonnycastle, Lori L 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 Burt, Amber A and Adam S Butterworth and Carey, David J 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 Cuellar-Partida, Gabriel and Danesh, John and Gail Davies and de Bakker, Paul I W and de Borst, Gert J and de Denus, Simon and de Groot, Mark C H and de Mutsert, Ren{\'e}e and Ian J Deary and George Dedoussis and Ellen W Demerath and Anneke I den Hollander and Joe G Dennis and Di Angelantonio, Emanuele and Drenos, Fotios and Du, Mengmeng and Dunning, Alison M and Easton, Douglas F and Ebeling, Tapani and Edwards, Todd L and Ellinor, Patrick T and Elliott, Paul and Evangelou, Evangelos and Farmaki, Aliki-Eleni and Jessica Faul and Feitosa, Mary F and Feng, Shuang and Ferrannini, Ele and Marco M Ferrario and Ferri{\`e}res, Jean and Florez, Jose C and Ford, Ian and Myriam Fornage and Franks, Paul W and Frikke-Schmidt, Ruth and Galesloot, Tessel E and Gan, Wei and Gandin, Ilaria and Paolo P. Gasparini and Giedraitis, Vilmantas and Giri, Ayush and Giorgia G Girotto and Gordon, Scott D and Gordon-Larsen, Penny and Gorski, Mathias and Grarup, Niels and Grove, Megan L and Gudnason, Vilmundur and Gustafsson, Stefan and Hansen, Torben and Kathleen Mullan Harris and Tamara B Harris and Andrew T Hattersley and Caroline Hayward and He, Liang and Iris M Heid and Heikkil{\"a}, Kauko and Helgeland, {\O}yvind and Hernesniemi, Jussi and Hewitt, Alex W and Lynne J Hocking and Hollensted, Mette and Oddgeir L Holmen and Hovingh, G Kees and Howson, Joanna M M and Hoyng, Carel B and Huang, Paul L and Hveem, Kristian 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 Jhun, Min A and Jia, Yucheng and Jiang, Xuejuan and Johansson, Stefan and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Jousilahti, Pekka 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 Kee, Frank and Keeman, Renske and Lambertus A Kiemeney and Kitajima, Hidetoshi and Kluivers, Kirsten B and Kocher, Thomas and Komulainen, Pirjo and Kontto, Jukka and Kooner, Jaspal S and Charles Kooperberg and Kovacs, Peter and Kriebel, Jennifer and Kuivaniemi, Helena and K{\"u}ry, S{\'e}bastien and Kuusisto, Johanna and La Bianca, Martina and Laakso, Markku and Lakka, Timo A and Lange, Ethan M and Leslie A Lange and Langefeld, Carl D and Langenberg, Claudia and Eric B Larson and Lee, I-Te and Lehtim{\"a}ki, Terho and Lewis, Cora E and Li, Huaixing and Li, Jin and Li-Gao, Ruifang and Lin, Honghuang and Lin, Li-An and Lin, Xu and Lars Lind and Lindstr{\"o}m, Jaana and Linneberg, Allan and Liu, Yeheng and Yongmei Liu and Lophatananon, Artitaya and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Lyytik{\"a}inen, Leo-Pekka and Mackey, David A and Pamela A F Madden and Alisa Manning and M{\"a}nnist{\"o}, Satu and Marenne, Ga{\"e}lle and Marten, Jonathan and Nicholas G Martin and Mazul, Angela L and Meidtner, Karina and Andres Metspalu and Mitchell, Paul and Mohlke, Karen L and Dennis O Mook-Kanamori and Morgan, Anna and Morris, Andrew D and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Michael A Nalls and Nauck, Matthias 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 Ntalla, Ioanna and Jeff O{\textquoteright}Connell and Oksa, Heikki and Loes M Olde Loohuis and Ophoff, Roel A and Owen, Katharine R and Packard, Chris J and Padmanabhan, Sandosh and Palmer, Colin N A 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 Person, Thomas N and Pirie, Ailith and Polasek, Ozren and Posthuma, Danielle and Olli T Raitakari and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Reiner, Alex P and Renstrom, Frida and Ridker, Paul M and Rioux, John D 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 Sandow, Kevin and Sapkota, Yadav and Sattar, Naveed and Schmidt, Marjanka K and Schreiner, Pamela J and Schulze, Matthias B and Scott, Robert A and Segura-Lepe, Marcelo P and Svati H Shah and Sim, Xueling and Sivapalaratnam, Suthesh and Small, Kerrin S and Albert Vernon Smith and Jennifer A Smith and Southam, Lorraine and Timothy Spector and Elizabeth K Speliotes and John M Starr and Steinthorsdottir, Valgerdur and Heather M Stringham and Stumvoll, Michael and Surendran, Praveen and {\textquoteright}t Hart, Leen M and Tansey, Katherine E and Tardif, Jean-Claude and Kent D Taylor and Teumer, Alexander and Thompson, Deborah J 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 Ulivi, Sheila and van der Laan, Sander W and Van Der Leij, Andries R and Cornelia M van Duijn and van Schoor, Natasja M and van Setten, Jessica and Varbo, Anette and Varga, Tibor V and Varma, Rohit and Digna R Velez Edwards and Vermeulen, Sita H and Vestergaard, Henrik and Vitart, Veronique and Vogt, Thomas F and Vozzi, Diego and Walker, Mark and Wang, Feijie and Wang, Carol A and Wang, Shuai and Wang, Yiqin and Wareham, Nicholas J and Warren, Helen R and Wessel, Jennifer and Willems, Sara M and Wilson, James G and Daniel Witte and Woods, Michael O 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 Jing Hua Zhao and Wei Zhao and Wei Zhao and Zheng, He and Zhou, Wei and Rotter, Jerome I and Boehnke, Michael and Kathiresan, Sekar and McCarthy, Mark I and Willer, Cristen J and Stefansson, Kari and Ingrid B Borecki and Liu, Dajiang J and Kari E North and Heard-Costa, Nancy L and Pers, Tune H and Lindgren, Cecilia M and Oxvig, Claus and Kutalik, Zolt{\'a}n and Fernando Rivadeneira and Ruth J F Loos and Timothy M Frayling and Joel N Hirschhron and Deloukas, Panos and Lettre, Guillaume}
}
