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

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Florence Demenais, Patricia Margaritte-Jeannin, Kathleen C. Barnes, William O. C. Cookson, Janine Altmueller, Wei Ang, R. Graham Barr, Terri H. Beaty, Allan B. Becker, John Beilby, Hans Bisgaard, Unnur Steina Bjornsdottir, Eugene Bleecker, Klaus Bonnelykke, Dorret I. Boomsma, Emmanuelle Bouzigon, Christopher E. Brightling, Myriam Brossard, Guy G. Brusselle, Esteban Burchard & 155 more Kristin M. Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Couto Alves, John A. Curtin, Adnan Custovic, Denise Daley, Johan C. de Jongste, Blanca E. Del-Rio-Navarro, Kathleen M. Donohue, Liesbeth Duijts, Celeste Eng, Johan G. Eriksson, Martin Farrall, Yuliya Fedorova, Bjarke Feenstra, Manuel A. Ferreira, Maxim B. Freidin, Zofia Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A. Gharib, Frank Gilliland, Raquel Granell, Penelope E. Graves, Daniel F. Gudbjartsson, Tari Haahtela, Susan R. Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliovaara, John Henderson, Blanca E. Himes, Hiroshi Hirose, Joel N. Hirschhorn, Albert Hofman, Patrick Holt, Jouke Hottenga, Thomas J. Hudson, Jennie Hui, Medea Imboden, Vladimir Ivanov, Vincent W. V. Jaddoe, Alan James, Christer Janson, Marjo-Riitta Jarvelin, Deborah Jarvis, Graham Jones, Ingileif Jonsdottir, Pekka Jousilahti, Michael Kabesch, Mika Kahonen, David B. Kantor, Alexandra S. Karunas, Elza Khusnutdinova, 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, Young-Ae Lee, Terho Lehtimaki, Sebastien Letort, Albert M. Levin, Guo Li, Liming Liang, Laura R. Loehr, Stephanie J. London, Daan W. Loth, Ani Manichaikul, Ingo Marenholz, Fernando J. Martinez, Melanie C. Matheson, Rasika A. Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L. McArdle, Mads Melbye, Erik Melen, Deborah Meyers, Sven Michel, Hamida Mohamdi, Arthur W. Musk, Rachel A. Myers, Maartje A. E. Nieuwenhuis, Emiko Noguchi, George T. O'Connor, Ludmila M. Ogorodova, Cameron D. Palmer, Aarno Palotie, Julie E. Park, Craig E. Pennell, Goran Pershagen, Alexey Polonikov, Dirkje S. Postma, Nicole Probst-Hensch, Valery P. Puzyrev, Benjamin A. Raby, Olli T. Raitakari, Adaikalavan Ramasamy, Stephen S. Rich, Colin F. Robertson, Isabelle Romieu, Muhammad T. Salam, Veikko Salomaa, Vivi Schlunssen, Robert Scott, Polina A. Selivanova, Torben Sigsgaard, Angela Simpson, Valerie Siroux, Lewis J. Smith, Maria Solodilova, Marie Standl, Kari Stefansson, David P. Strachan, Bruno H. Stricker, Atsushi Takahashi, Philip J. Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Carla M. T. Tiesler, Dara G. Torgerson, Tatsuhiko Tsunoda, Andre G. Uitterlinden, Ralf J. P. van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M. Vonk, Johannes Waage, Nick J. Wareham, Scott T. Weiss, Wendy B. White, Magnus Wickman, Elisabeth Widen, Gonneke Willemsen, L. Keoki Williams, Inge M. Wouters, James J. Yang, Jing Hua Zhao, Miriam F. Moffatt, Carole Ober, Dan L. Nicolae

Original languageEnglish
Pages (from-to)42-53
JournalNature Genetics
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2018

King's Authors

Abstract

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.

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