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J</style></author><author><style face="normal" font="default" size="100%">Elliott, Paul</style></author><author><style face="normal" font="default" size="100%">Rice, Kenneth</style></author><author><style face="normal" font="default" size="100%">Munroe, Patricia B</style></author><author><style face="normal" font="default" size="100%">Morrison, Alanna C</style></author><author><style face="normal" font="default" size="100%">Cupples, L Adrienne</style></author><author><style face="normal" font="default" size="100%">Rao, Dabeeru C</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">CHARGE Neurology Working Group</style></author><author><style face="normal" font="default" size="100%">COGENT-Kidney Consortium</style></author><author><style face="normal" font="default" size="100%">GIANT Consortium</style></author><author><style face="normal" font="default" size="100%">LifeLines Cohort Study</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hum. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Blood Pressure</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Continental Population Groups</style></keyword><keyword><style  face="normal" font="default" size="100%">Diastole</style></keyword><keyword><style  face="normal" font="default" size="100%">Epistasis, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Reproducibility of Results</style></keyword><keyword><style  face="normal" font="default" size="100%">Smoking</style></keyword><keyword><style  face="normal" font="default" size="100%">Systole</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 03 01</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">102</style></volume><pages><style face="normal" font="default" size="100%">375-400</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p &lt; 5 × 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p &lt; 5 × 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/29455858?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Marouli, Eirini</style></author><author><style face="normal" font="default" size="100%">Graff, Mariaelisa</style></author><author><style face="normal" font="default" size="100%">Medina-Gomez, Carolina</style></author><author><style face="normal" font="default" size="100%">Lo, Ken Sin</style></author><author><style face="normal" font="default" size="100%">Wood, Andrew R</style></author><author><style face="normal" font="default" size="100%">Kjaer, Troels R</style></author><author><style face="normal" font="default" size="100%">Fine, Rebecca S</style></author><author><style face="normal" font="default" size="100%">Lu, Yingchang</style></author><author><style face="normal" font="default" size="100%">Schurmann, Claudia</style></author><author><style face="normal" font="default" size="100%">Highland, Heather M</style></author><author><style face="normal" font="default" size="100%">Rüeger, Sina</style></author><author><style face="normal" font="default" size="100%">Thorleifsson, Gudmar</style></author><author><style face="normal" font="default" size="100%">Justice, Anne E</style></author><author><style face="normal" font="default" size="100%">Lamparter, David</style></author><author><style face="normal" font="default" size="100%">Stirrups, Kathleen E</style></author><author><style face="normal" font="default" size="100%">Turcot, Valérie</style></author><author><style face="normal" font="default" size="100%">Young, Kristin L</style></author><author><style face="normal" font="default" size="100%">Winkler, Thomas W</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Karaderi, Tugce</style></author><author><style face="normal" font="default" size="100%">Locke, Adam E</style></author><author><style face="normal" font="default" size="100%">Masca, Nicholas G D</style></author><author><style face="normal" font="default" size="100%">Ng, Maggie C Y</style></author><author><style face="normal" font="default" size="100%">Mudgal, Poorva</style></author><author><style face="normal" font="default" size="100%">Rivas, Manuel A</style></author><author><style face="normal" font="default" size="100%">Vedantam, Sailaja</style></author><author><style face="normal" font="default" size="100%">Mahajan, Anubha</style></author><author><style face="normal" font="default" size="100%">Guo, Xiuqing</style></author><author><style face="normal" font="default" size="100%">Abecasis, Goncalo</style></author><author><style face="normal" font="default" size="100%">Aben, Katja K</style></author><author><style face="normal" font="default" size="100%">Adair, Linda S</style></author><author><style face="normal" font="default" size="100%">Alam, Dewan S</style></author><author><style face="normal" font="default" size="100%">Albrecht, Eva</style></author><author><style face="normal" font="default" size="100%">Allin, Kristine H</style></author><author><style face="normal" font="default" size="100%">Allison, Matthew</style></author><author><style face="normal" font="default" size="100%">Amouyel, Philippe</style></author><author><style face="normal" font="default" size="100%">Appel, Emil V</style></author><author><style face="normal" font="default" size="100%">Arveiler, Dominique</style></author><author><style face="normal" font="default" size="100%">Asselbergs, Folkert W</style></author><author><style face="normal" font="default" size="100%">Auer, Paul L</style></author><author><style face="normal" font="default" size="100%">Balkau, Beverley</style></author><author><style face="normal" font="default" size="100%">Banas, Bernhard</style></author><author><style face="normal" font="default" size="100%">Bang, Lia E</style></author><author><style face="normal" font="default" size="100%">Benn, Marianne</style></author><author><style face="normal" font="default" size="100%">Bergmann, Sven</style></author><author><style face="normal" font="default" size="100%">Bielak, Lawrence F</style></author><author><style face="normal" font="default" size="100%">Blüher, Matthias</style></author><author><style face="normal" font="default" size="100%">Boeing, Heiner</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Böger, Carsten A</style></author><author><style face="normal" font="default" size="100%">Bonnycastle, Lori L</style></author><author><style face="normal" font="default" size="100%">Bork-Jensen, Jette</style></author><author><style face="normal" font="default" size="100%">Bots, Michiel L</style></author><author><style face="normal" font="default" size="100%">Bottinger, Erwin P</style></author><author><style face="normal" font="default" size="100%">Bowden, Donald W</style></author><author><style face="normal" font="default" size="100%">Brandslund, Ivan</style></author><author><style face="normal" font="default" size="100%">Breen, Gerome</style></author><author><style face="normal" font="default" size="100%">Brilliant, Murray H</style></author><author><style face="normal" font="default" size="100%">Broer, Linda</style></author><author><style face="normal" font="default" size="100%">Burt, Amber A</style></author><author><style face="normal" font="default" size="100%">Butterworth, Adam S</style></author><author><style face="normal" font="default" size="100%">Carey, David J</style></author><author><style face="normal" font="default" size="100%">Caulfield, Mark J</style></author><author><style face="normal" font="default" size="100%">Chambers, John C</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">Chen, Yii-Der Ida</style></author><author><style face="normal" font="default" size="100%">Chowdhury, Rajiv</style></author><author><style face="normal" font="default" size="100%">Christensen, Cramer</style></author><author><style face="normal" font="default" size="100%">Chu, Audrey Y</style></author><author><style face="normal" font="default" size="100%">Cocca, Massimiliano</style></author><author><style face="normal" font="default" size="100%">Collins, Francis 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H</style></author><author><style face="normal" font="default" size="100%">de Mutsert, Renée</style></author><author><style face="normal" font="default" size="100%">Deary, Ian J</style></author><author><style face="normal" font="default" size="100%">Dedoussis, George</style></author><author><style face="normal" font="default" size="100%">Demerath, Ellen W</style></author><author><style face="normal" font="default" size="100%">den Hollander, Anneke I</style></author><author><style face="normal" font="default" size="100%">Dennis, Joe G</style></author><author><style face="normal" font="default" size="100%">Di Angelantonio, Emanuele</style></author><author><style face="normal" font="default" size="100%">Drenos, Fotios</style></author><author><style face="normal" font="default" size="100%">Du, Mengmeng</style></author><author><style face="normal" font="default" size="100%">Dunning, Alison M</style></author><author><style face="normal" font="default" size="100%">Easton, Douglas F</style></author><author><style face="normal" font="default" size="100%">Ebeling, Tapani</style></author><author><style face="normal" font="default" size="100%">Edwards, Todd L</style></author><author><style face="normal" font="default" size="100%">Ellinor, Patrick T</style></author><author><style face="normal" font="default" size="100%">Elliott, Paul</style></author><author><style face="normal" font="default" size="100%">Evangelou, Evangelos</style></author><author><style face="normal" font="default" size="100%">Farmaki, Aliki-Eleni</style></author><author><style face="normal" font="default" size="100%">Faul, Jessica D</style></author><author><style face="normal" font="default" size="100%">Feitosa, Mary F</style></author><author><style face="normal" font="default" size="100%">Feng, Shuang</style></author><author><style face="normal" font="default" size="100%">Ferrannini, Ele</style></author><author><style face="normal" font="default" size="100%">Ferrario, Marco M</style></author><author><style face="normal" font="default" size="100%">Ferrières, Jean</style></author><author><style face="normal" font="default" size="100%">Florez, Jose C</style></author><author><style face="normal" font="default" size="100%">Ford, Ian</style></author><author><style face="normal" font="default" size="100%">Fornage, Myriam</style></author><author><style face="normal" font="default" size="100%">Franks, Paul W</style></author><author><style face="normal" font="default" size="100%">Frikke-Schmidt, Ruth</style></author><author><style face="normal" font="default" size="100%">Galesloot, Tessel E</style></author><author><style face="normal" font="default" size="100%">Gan, Wei</style></author><author><style face="normal" font="default" size="100%">Gandin, Ilaria</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Giedraitis, Vilmantas</style></author><author><style face="normal" font="default" size="100%">Giri, Ayush</style></author><author><style face="normal" font="default" size="100%">Girotto, Giorgia</style></author><author><style face="normal" font="default" size="100%">Gordon, Scott D</style></author><author><style face="normal" font="default" size="100%">Gordon-Larsen, Penny</style></author><author><style face="normal" font="default" size="100%">Gorski, Mathias</style></author><author><style face="normal" font="default" size="100%">Grarup, Niels</style></author><author><style face="normal" font="default" size="100%">Grove, Megan L</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Gustafsson, Stefan</style></author><author><style face="normal" font="default" size="100%">Hansen, Torben</style></author><author><style face="normal" font="default" size="100%">Harris, Kathleen Mullan</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hattersley, Andrew T</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">He, Liang</style></author><author><style face="normal" font="default" size="100%">Heid, Iris M</style></author><author><style face="normal" font="default" size="100%">Heikkilä, Kauko</style></author><author><style face="normal" font="default" size="100%">Helgeland, Øyvind</style></author><author><style face="normal" font="default" size="100%">Hernesniemi, Jussi</style></author><author><style face="normal" font="default" size="100%">Hewitt, Alex W</style></author><author><style face="normal" font="default" size="100%">Hocking, Lynne J</style></author><author><style face="normal" font="default" size="100%">Hollensted, Mette</style></author><author><style face="normal" font="default" size="100%">Holmen, Oddgeir L</style></author><author><style face="normal" font="default" size="100%">Hovingh, G Kees</style></author><author><style face="normal" font="default" size="100%">Howson, Joanna M M</style></author><author><style face="normal" font="default" size="100%">Hoyng, Carel B</style></author><author><style face="normal" font="default" size="100%">Huang, Paul L</style></author><author><style face="normal" font="default" size="100%">Hveem, Kristian</style></author><author><style face="normal" font="default" size="100%">Ikram, M Arfan</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Jackson, Anne U</style></author><author><style face="normal" font="default" size="100%">Jansson, Jan-Håkan</style></author><author><style face="normal" font="default" size="100%">Jarvik, Gail P</style></author><author><style face="normal" font="default" size="100%">Jensen, Gorm B</style></author><author><style face="normal" font="default" size="100%">Jhun, Min A</style></author><author><style face="normal" font="default" size="100%">Jia, Yucheng</style></author><author><style face="normal" font="default" size="100%">Jiang, Xuejuan</style></author><author><style face="normal" font="default" size="100%">Johansson, Stefan</style></author><author><style face="normal" font="default" size="100%">Jørgensen, Marit E</style></author><author><style face="normal" font="default" size="100%">Jørgensen, Torben</style></author><author><style face="normal" font="default" size="100%">Jousilahti, Pekka</style></author><author><style face="normal" font="default" size="100%">Jukema, J Wouter</style></author><author><style face="normal" font="default" size="100%">Kahali, Bratati</style></author><author><style face="normal" font="default" size="100%">Kahn, René S</style></author><author><style face="normal" font="default" size="100%">Kähönen, Mika</style></author><author><style face="normal" font="default" size="100%">Kamstrup, Pia R</style></author><author><style face="normal" font="default" size="100%">Kanoni, Stavroula</style></author><author><style face="normal" font="default" size="100%">Kaprio, Jaakko</style></author><author><style face="normal" font="default" size="100%">Karaleftheri, Maria</style></author><author><style face="normal" font="default" size="100%">Kardia, Sharon L R</style></author><author><style face="normal" font="default" size="100%">Karpe, Fredrik</style></author><author><style face="normal" font="default" size="100%">Kee, Frank</style></author><author><style face="normal" font="default" size="100%">Keeman, Renske</style></author><author><style face="normal" font="default" size="100%">Kiemeney, Lambertus A</style></author><author><style face="normal" font="default" size="100%">Kitajima, Hidetoshi</style></author><author><style face="normal" font="default" size="100%">Kluivers, Kirsten B</style></author><author><style face="normal" font="default" size="100%">Kocher, Thomas</style></author><author><style face="normal" font="default" size="100%">Komulainen, Pirjo</style></author><author><style face="normal" font="default" size="100%">Kontto, Jukka</style></author><author><style face="normal" font="default" size="100%">Kooner, Jaspal S</style></author><author><style face="normal" font="default" size="100%">Kooperberg, Charles</style></author><author><style face="normal" font="default" size="100%">Kovacs, Peter</style></author><author><style face="normal" font="default" size="100%">Kriebel, Jennifer</style></author><author><style face="normal" font="default" size="100%">Kuivaniemi, Helena</style></author><author><style face="normal" font="default" size="100%">Küry, Sébastien</style></author><author><style face="normal" font="default" size="100%">Kuusisto, Johanna</style></author><author><style face="normal" font="default" size="100%">La Bianca, Martina</style></author><author><style face="normal" font="default" size="100%">Laakso, Markku</style></author><author><style face="normal" font="default" size="100%">Lakka, Timo A</style></author><author><style face="normal" font="default" size="100%">Lange, Ethan M</style></author><author><style face="normal" font="default" size="100%">Lange, Leslie A</style></author><author><style face="normal" font="default" size="100%">Langefeld, Carl D</style></author><author><style face="normal" font="default" size="100%">Langenberg, Claudia</style></author><author><style face="normal" font="default" size="100%">Larson, Eric B</style></author><author><style face="normal" font="default" size="100%">Lee, I-Te</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho</style></author><author><style face="normal" font="default" size="100%">Lewis, Cora E</style></author><author><style face="normal" font="default" size="100%">Li, Huaixing</style></author><author><style face="normal" font="default" size="100%">Li, 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font="default" size="100%">Lubitz, Steven A</style></author><author><style face="normal" font="default" size="100%">Lyytikäinen, Leo-Pekka</style></author><author><style face="normal" font="default" size="100%">Mackey, David A</style></author><author><style face="normal" font="default" size="100%">Madden, Pamela A F</style></author><author><style face="normal" font="default" size="100%">Manning, Alisa K</style></author><author><style face="normal" font="default" size="100%">Männistö, Satu</style></author><author><style face="normal" font="default" size="100%">Marenne, Gaëlle</style></author><author><style face="normal" font="default" size="100%">Marten, Jonathan</style></author><author><style face="normal" font="default" size="100%">Martin, Nicholas G</style></author><author><style face="normal" font="default" size="100%">Mazul, Angela L</style></author><author><style face="normal" font="default" size="100%">Meidtner, Karina</style></author><author><style face="normal" font="default" 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font="default" size="100%">van Schoor, Natasja M</style></author><author><style face="normal" font="default" size="100%">van Setten, Jessica</style></author><author><style face="normal" font="default" size="100%">Varbo, Anette</style></author><author><style face="normal" font="default" size="100%">Varga, Tibor V</style></author><author><style face="normal" font="default" size="100%">Varma, Rohit</style></author><author><style face="normal" font="default" size="100%">Edwards, Digna R Velez</style></author><author><style face="normal" font="default" size="100%">Vermeulen, Sita H</style></author><author><style face="normal" font="default" size="100%">Vestergaard, Henrik</style></author><author><style face="normal" font="default" size="100%">Vitart, Veronique</style></author><author><style face="normal" font="default" size="100%">Vogt, Thomas F</style></author><author><style face="normal" font="default" size="100%">Vozzi, Diego</style></author><author><style face="normal" font="default" size="100%">Walker, Mark</style></author><author><style face="normal" font="default" size="100%">Wang, Feijie</style></author><author><style face="normal" font="default" size="100%">Wang, Carol A</style></author><author><style face="normal" font="default" size="100%">Wang, Shuai</style></author><author><style face="normal" font="default" size="100%">Wang, Yiqin</style></author><author><style face="normal" font="default" size="100%">Wareham, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Warren, Helen R</style></author><author><style face="normal" font="default" size="100%">Wessel, Jennifer</style></author><author><style face="normal" font="default" size="100%">Willems, Sara M</style></author><author><style face="normal" font="default" size="100%">Wilson, James G</style></author><author><style face="normal" font="default" size="100%">Witte, Daniel R</style></author><author><style face="normal" font="default" size="100%">Woods, Michael 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font="default" size="100%">Zhao, Wei</style></author><author><style face="normal" font="default" size="100%">Zheng, He</style></author><author><style face="normal" font="default" size="100%">Zhou, Wei</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Boehnke, Michael</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author><author><style face="normal" font="default" size="100%">McCarthy, Mark I</style></author><author><style face="normal" font="default" size="100%">Willer, Cristen J</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Borecki, Ingrid B</style></author><author><style face="normal" font="default" size="100%">Liu, Dajiang J</style></author><author><style face="normal" font="default" size="100%">North, Kari E</style></author><author><style face="normal" font="default" size="100%">Heard-Costa, Nancy L</style></author><author><style face="normal" font="default" size="100%">Pers, Tune H</style></author><author><style face="normal" font="default" size="100%">Lindgren, Cecilia M</style></author><author><style face="normal" font="default" size="100%">Oxvig, Claus</style></author><author><style face="normal" font="default" size="100%">Kutalik, Zoltán</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Frayling, Timothy M</style></author><author><style face="normal" font="default" size="100%">Hirschhorn, Joel N</style></author><author><style face="normal" font="default" size="100%">Deloukas, Panos</style></author><author><style face="normal" font="default" size="100%">Lettre, Guillaume</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">EPIC-InterAct Consortium</style></author><author><style face="normal" font="default" size="100%">CHD Exome+ Consortium</style></author><author><style face="normal" font="default" size="100%">ExomeBP Consortium</style></author><author><style face="normal" font="default" size="100%">T2D-Genes Consortium</style></author><author><style face="normal" font="default" size="100%">GoT2D Genes Consortium</style></author><author><style face="normal" font="default" size="100%">Global Lipids Genetics Consortium</style></author><author><style face="normal" font="default" size="100%">ReproGen Consortium</style></author><author><style face="normal" font="default" size="100%">MAGIC Investigators</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Rare and low-frequency coding variants alter human adult height.</style></title><secondary-title><style face="normal" font="default" size="100%">Nature</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nature</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">ADAMTS Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Height</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Adhesion Molecules</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Glycoproteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Glycosaminoglycans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hedgehog Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Intercellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Interferon Regulatory Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Interleukin-11 Receptor alpha Subunit</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword><keyword><style  face="normal" font="default" size="100%">NADPH Oxidase 4</style></keyword><keyword><style  face="normal" font="default" size="100%">NADPH Oxidases</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Pregnancy-Associated Plasma Protein-A</style></keyword><keyword><style  face="normal" font="default" size="100%">Procollagen N-Endopeptidase</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteoglycans</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteolysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Androgen</style></keyword><keyword><style  face="normal" font="default" size="100%">Somatomedins</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 02 09</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">542</style></volume><pages><style face="normal" font="default" size="100%">186-190</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7640</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract</style></custom1></record></records></xml>