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

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.

SUBMITTER: Demenais F 

PROVIDER: S-EPMC5901974 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Demenais Florence F   Margaritte-Jeannin Patricia P   Barnes Kathleen C KC   Cookson William O C WOC   Altmüller Janine J   Ang Wei W   Barr R Graham RG   Beaty Terri H TH   Becker Allan B AB   Beilby John J   Bisgaard Hans H   Bjornsdottir Unnur Steina US   Bleecker Eugene E   Bønnelykke Klaus K   Boomsma Dorret I DI   Bouzigon Emmanuelle E   Brightling Christopher E CE   Brossard Myriam M   Brusselle Guy G GG   Burchard Esteban E   Burkart Kristin M KM   Bush Andrew A   Chan-Yeung Moira M   Chung Kian Fan KF   Couto Alves Alexessander A   Curtin John A JA   Custovic Adnan A   Daley Denise D   de Jongste Johan C JC   Del-Rio-Navarro Blanca E BE   Donohue Kathleen M KM   Duijts Liesbeth L   Eng Celeste C   Eriksson Johan G JG   Farrall Martin M   Fedorova Yuliya Y   Feenstra Bjarke B   Ferreira Manuel A MA   Freidin Maxim B MB   Gajdos Zofia Z   Gauderman Jim J   Gehring Ulrike U   Geller Frank F   Genuneit Jon J   Gharib Sina A SA   Gilliland Frank F   Granell Raquel R   Graves Penelope E PE   Gudbjartsson Daniel F DF   Haahtela Tari T   Heckbert Susan R SR   Heederik Dick D   Heinrich Joachim J   Heliövaara Markku M   Henderson John J   Himes Blanca E BE   Hirose Hiroshi H   Hirschhorn Joel N JN   Hofman Albert A   Holt Patrick P   Hottenga Jouke J   Hudson Thomas J TJ   Hui Jennie J   Imboden Medea M   Ivanov Vladimir V   Jaddoe Vincent W V VWV   James Alan A   Janson Christer C   Jarvelin Marjo-Riitta MR   Jarvis Deborah D   Jones Graham G   Jonsdottir Ingileif I   Jousilahti Pekka P   Kabesch Michael M   Kähönen Mika M   Kantor David B DB   Karunas Alexandra S AS   Khusnutdinova Elza E   Koppelman Gerard H GH   Kozyrskyj Anita L AL   Kreiner Eskil E   Kubo Michiaki M   Kumar Rajesh R   Kumar Ashish A   Kuokkanen Mikko M   Lahousse Lies L   Laitinen Tarja T   Laprise Catherine C   Lathrop Mark M   Lau Susanne S   Lee Young-Ae YA   Lehtimäki Terho T   Letort Sébastien S   Levin Albert M AM   Li Guo G   Liang Liming L   Loehr Laura R LR   London Stephanie J SJ   Loth Daan W DW   Manichaikul Ani A   Marenholz Ingo I   Martinez Fernando J FJ   Matheson Melanie C MC   Mathias Rasika A RA   Matsumoto Kenji K   Mbarek Hamdi H   McArdle Wendy L WL   Melbye Mads M   Melén Erik E   Meyers Deborah D   Michel Sven S   Mohamdi Hamida H   Musk Arthur W AW   Myers Rachel A RA   Nieuwenhuis Maartje A E MAE   Noguchi Emiko E   O'Connor George T GT   Ogorodova Ludmila M LM   Palmer Cameron D CD   Palotie Aarno A   Park Julie E JE   Pennell Craig E CE   Pershagen Göran G   Polonikov Alexey A   Postma Dirkje S DS   Probst-Hensch Nicole N   Puzyrev Valery P VP   Raby Benjamin A BA   Raitakari Olli T OT   Ramasamy Adaikalavan A   Rich Stephen S SS   Robertson Colin F CF   Romieu Isabelle I   Salam Muhammad T MT   Salomaa Veikko V   Schlünssen Vivi V   Scott Robert R   Selivanova Polina A PA   Sigsgaard Torben T   Simpson Angela A   Siroux Valérie V   Smith Lewis J LJ   Solodilova Maria M   Standl Marie M   Stefansson Kari K   Strachan David P DP   Stricker Bruno H BH   Takahashi Atsushi A   Thompson Philip J PJ   Thorleifsson Gudmar G   Thorsteinsdottir Unnur U   Tiesler Carla M T CMT   Torgerson Dara G DG   Tsunoda Tatsuhiko T   Uitterlinden André G AG   van der Valk Ralf J P RJP   Vaysse Amaury A   Vedantam Sailaja S   von Berg Andrea A   von Mutius Erika E   Vonk Judith M JM   Waage Johannes J   Wareham Nick J NJ   Weiss Scott T ST   White Wendy B WB   Wickman Magnus M   Widén Elisabeth E   Willemsen Gonneke G   Williams L Keoki LK   Wouters Inge M IM   Yang James J JJ   Zhao Jing Hua JH   Moffatt Miriam F MF   Ober Carole C   Nicolae Dan L DL  

Nature genetics 20171222 1

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 i  ...[more]

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