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

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 BurchardKristin 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, Susan R Heckbert, Jouke Hottenga, Hamdi Mbarek, Gonneke Willemsen, Australian Asthma Genetics Consortium (AAGC) collaborators

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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.

Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalNature Genetics
Volume50
Issue number1
Early online date22 Dec 2017
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Journal Article

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