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

Authors:
Sina A Gharib, MD
Sina A Gharib, MD
Center for Lung Biology, UW Medicine Sleep Center, University of Washington
Associate Professor
Seattle, WA | United States
Florence Demenais Patricia Margaritte-Jeannin Kathleen C Barnes William O C Cookson Janine Altmüller Wei Ang R Graham Barr Terri H Beaty Allan B Becker John Beilby Hans Bisgaard Unnur Steina Bjornsdottir Eugene Bleecker Klaus Bønnelykke Dorret I Boomsma Emmanuelle Bouzigon Christopher E Brightling Myriam Brossard Guy G Brusselle Esteban Burchard 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 Frank Gilliland Raquel Granell Penelope E Graves Daniel F Gudbjartsson Tari Haahtela Susan R Heckbert Dick Heederik Joachim Heinrich Markku Heliövaara 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 Kähönen 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 Lehtimäki Sébastien 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 Melén 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 Göran 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 Schlünssen Robert Scott Polina A Selivanova Torben Sigsgaard Angela Simpson Valérie 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 André 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 Widén Gonneke Willemsen L Keoki Williams Inge M Wouters James J Yang Jing Hua Zhao Miriam F Moffatt Carole Ober Dan L Nicolae

Nat Genet 2018 01 22;50(1):42-53. Epub 2017 Dec 22.

Departments of Statistics, Human Genetics and Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.

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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http://www.nature.com/articles/s41588-017-0014-7
Publisher Site
http://dx.doi.org/10.1038/s41588-017-0014-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901974PMC
January 2018
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