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Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

2017; Nature Portfolio; Volume: 50; Issue: 1 Linguagem: Inglês

10.1038/s41588-017-0014-7

1546-1718

Florence Démenais, Patricia Margaritte‐Jeannin, Kathleen C. Barnes, William Cookson, Janine Altmüller, Wei Ang, R. Graham Barr, Terri H. Beaty, Allan B. Becker, John Beilby, Hans Bisgaard, Unnur Steina Björnsdóttir, Eugene R. Bleecker, Klaus Bønnelykke, Dorret I. Boomsma, Emmanuelle Bouzigon, Christopher E. Brightling, Myriam Brossard, Guy Brusselle, Esteban G. Burchard, Kristin M. Burkart, Andrew Bush, Moira Chan‐Yeung, Kian Fan Chung, Alexessander Couto Alves, John A. Curtin, Adnan Ćustović, Denise Daley, Johan C. de Jongste, Blanca E. Del‐Rio‐Navarro, Kathleen Donohue, Liesbeth Duijts, Celeste Eng, Johan G. Eriksson, Martin Farrall, Yu. Yu. Fedorova, Bjarke Feenstra, Manuel A. R. Ferreira, Maxim B. Freidin, Zofia K. Z. Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A. Gharib, Frank D. Gilliland, Raquel Granell, Penelope E. Graves, Daníel F. Guðbjartsson, Tari Haahtela, Susan R. Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliövaara, John Henderson, Blanca E. Himes, Hiroshi Hirose, Joel N. Hirschhorn, Albert Hofman, Patrick G. Holt, Jouke‐Jan Hottenga, Thomas J. Hudson, Jennie Hui, Medea Imboden, В. П. Иванов, Vincent W. V. Jaddoe, Anthony James, Christer Janson, Marjo‐Riitta Järvelin, Deborah Jarvis, Graham Jones, Ingileif Jónsdóttir, Jari Lahti, Michael Kabesch, Mika Kähönen, David B. Kantor, А. С. Карунас, Э. К. Хуснутдинова, Gerard H. Koppelman, Anita L. Kozyrskyj, Eskil Kreiner, Michiaki Kubo, Rajesh Kumar, Ashish Kumar, Mikko Kuokkanen, Lies Lahousse, Tarja Laitinen, Catherine Laprise, Mark Lathrop, Susanne Lau, Youngae Lee, Terho Lehtimäki, Sébastien Letort, Albert M. Levin, Li Guo, Liming Liang, Laura R. Loehr, Stephanie J. London, Daan W. Loth, Ani Manichaikul, Ingo Marenholz, Fernando J. Martínez, Melanie C. Matheson, Rasika A. Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L. McArdle, Mads Melbye, Erik Melén, Deborah A. Meyers, Sven Michel, Hamida Mohamdi, Arthur W. Musk, Rachel A. Myers, Maartje A. E. Nieuwenhuis, Emiko Noguchi, George O'connor, Л. М. Огородова, Cameron D. Palmer, Aarno Palotie, Julie E. Park, Craig E. Pennell, Göran Pershagen, Alexey Polonikov, Dirkje S. Postma, Nicole Probst‐Hensch, В. П. Пузырев, Benjamin A. Raby, Olli T. Raitakari, Adaikalavan Ramasamy, Stephen S. Rich, Colin F. Robertson, Isabelle Romieu, Muhammad T. Salam, Veikko Salomaa, Vivi Schlünssen, Robert A. Scott, П. А. Селиванова, Torben Sigsgaard, Angela Simpson, Valérie Siroux, Lewis J. Smith, Maria Solodilova, Marie Standl, Hreinn Stefánsson, David P. Strachan, Bruno H. Stricker, Atsushi Takahashi, Philip J. Thompson, Guðmar Þorleifsson, Unnur Þorsteinsdóttir, Carla M. T. Tiesler, Dara G. Torgerson, Tatsuhiko Tsunoda, André G. Uitterlinden, Ralf J.P. van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M. Vonk, Johannes Waage, Nicholas J. Wareham, Scott T. Weiss, Wendy White, Magnus Wickman, Elisabeth Widén, Gonneke Willemsen, L. Keoki Williams, Inge M. Wouters, James J. Yang, Jing Hua Zhao, Miriam F. Moffatt, Carole Ober, Dan L. Nicolae,

Genetic Associations and Epidemiology

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms. The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.