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

Australian Asthma Genetics Consortium Collaborators

doi:10.1038/s41588-017-0014-7

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

Australian Asthma Genetics Consortium Collaborators

Research output: Contribution to journal › Article › peer-review

264 Citations (Scopus)

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 language	English
Pages (from-to)	42-50
Number of pages	9
Journal	Nature Genetics
Volume	50
Issue number	1
DOIs	https://doi.org/10.1038/s41588-017-0014-7
Publication status	Published - 1 Jan 2018

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10.1038/s41588-017-0014-7

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901974/

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@article{723cd008fb1a490c9177a72f80102307,

title = "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.",

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

year = "2018",

month = jan,

day = "1",

doi = "10.1038/s41588-017-0014-7",

language = "English",

volume = "50",

pages = "42--50",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "1",

}

TY - JOUR

T1 - Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

AU - Australian Asthma Genetics Consortium Collaborators

AU - Demenais, Florence

AU - Margaritte-Jeannin, Patricia

AU - Barnes, Kathleen C.

AU - Cookson, William O.C.

AU - Altmüller, Janine

AU - Ang, Wei

AU - Barr, R. Graham

AU - Beaty, Terri H.

AU - Becker, Allan B.

AU - Beilby, John

AU - Bisgaard, Hans

AU - Bjornsdottir, Unnur Steina

AU - Bleecker, Eugene

AU - Bønnelykke, Klaus

AU - Boomsma, Dorret I.

AU - Bouzigon, Emmanuelle

AU - Brightling, Christopher E.

AU - Brossard, Myriam

AU - Brusselle, Guy G.

AU - Burchard, Esteban

AU - Burkart, Kristin M.

AU - Bush, Andrew

AU - Chan-Yeung, Moira

AU - Chung, Kian Fan

AU - Couto Alves, Alexessander

AU - Curtin, John A.

AU - Custovic, Adnan

AU - Daley, Denise

AU - De Jongste, Johan C.

AU - Del-Rio-Navarro, Blanca E.

AU - Donohue, Kathleen M.

AU - Duijts, Liesbeth

AU - Eng, Celeste

AU - Eriksson, Johan G.

AU - Farrall, Martin

AU - Fedorova, Yuliya

AU - Feenstra, Bjarke

AU - Ferreira, Manuel A.

AU - Freidin, Maxim B.

AU - Gajdos, Zofia

AU - Gauderman, Jim

AU - Gehring, Ulrike

AU - Geller, Frank

AU - Genuneit, Jon

AU - Gharib, Sina A.

AU - Gilliland, Frank

AU - Granell, Raquel

AU - Graves, Penelope E.

AU - Gudbjartsson, Daniel F.

AU - Haahtela, Tari

AU - Heckbert, Susan R.

AU - Heederik, Dick

AU - Heinrich, Joachim

AU - Heliövaara, Markku

AU - Henderson, John

AU - Himes, Blanca E.

AU - Hirose, Hiroshi

AU - Hirschhorn, Joel N.

AU - Hofman, Albert

AU - Holt, Patrick

AU - Hottenga, Jouke

AU - Hudson, Thomas J.

AU - Hui, Jennie

AU - Imboden, Medea

AU - Ivanov, Vladimir

AU - Jaddoe, Vincent W.V.

AU - James, Alan

AU - Janson, Christer

AU - Jarvelin, Marjo Riitta

AU - Jarvis, Deborah

AU - Jones, Graham

AU - Jonsdottir, Ingileif

AU - Jousilahti, Pekka

AU - Kabesch, Michael

AU - Kähönen, Mika

AU - Kantor, David B.

AU - Karunas, Alexandra S.

AU - Khusnutdinova, Elza

AU - Koppelman, Gerard H.

AU - Kozyrskyj, Anita L.

AU - Kreiner, Eskil

AU - Kubo, Michiaki

AU - Kumar, Rajesh

AU - Kumar, Ashish

AU - Kuokkanen, Mikko

AU - Lahousse, Lies

AU - Laitinen, Tarja

AU - Laprise, Catherine

AU - Lathrop, Mark

AU - Lau, Susanne

AU - Lee, Young Ae

AU - Lehtimäki, Terho

AU - Letort, Sébastien

AU - Levin, Albert M.

AU - Li, Guo

AU - Liang, Liming

AU - Loehr, Laura R.

AU - London, Stephanie J.

AU - Loth, Daan W.

AU - Manichaikul, Ani

AU - Marenholz, Ingo

AU - Martinez, Fernando J.

AU - Matheson, Melanie C.

AU - Mathias, Rasika A.

AU - Matsumoto, Kenji

AU - Mbarek, Hamdi

AU - McArdle, Wendy L.

AU - Melbye, Mads

AU - Melén, Erik

AU - Meyers, Deborah

AU - Michel, Sven

AU - Mohamdi, Hamida

AU - Musk, Arthur W.

AU - Myers, Rachel A.

AU - Nieuwenhuis, Maartje A.E.

AU - Noguchi, Emiko

AU - O'Connor, George T.

AU - Ogorodova, Ludmila M.

AU - Palmer, Cameron D.

AU - Palotie, Aarno

AU - Park, Julie E.

AU - Pennell, Craig E.

AU - Pershagen, Göran

AU - Polonikov, Alexey

AU - Postma, Dirkje S.

AU - Probst-Hensch, Nicole

AU - Puzyrev, Valery P.

AU - Raby, Benjamin A.

AU - Raitakari, Olli T.

AU - Ramasamy, Adaikalavan

AU - Rich, Stephen S.

AU - Robertson, Colin F.

AU - Romieu, Isabelle

AU - Salam, Muhammad T.

AU - Salomaa, Veikko

AU - Schlünssen, Vivi

AU - Scott, Robert

AU - Selivanova, Polina A.

AU - Sigsgaard, Torben

AU - Simpson, Angela

AU - Siroux, Valérie

AU - Smith, Lewis J.

AU - Solodilova, Maria

AU - Standl, Marie

AU - Stefansson, Kari

AU - Strachan, David P.

AU - Stricker, Bruno H.

AU - Takahashi, Atsushi

AU - Thompson, Philip J.

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Tiesler, Carla M.T.

AU - Torgerson, Dara G.

AU - Tsunoda, Tatsuhiko

AU - Uitterlinden, André G.

AU - Van Der Valk, Ralf J.P.

AU - Vaysse, Amaury

AU - Vedantam, Sailaja

AU - Von Berg, Andrea

AU - Von Mutius, Erika

AU - Vonk, Judith M.

AU - Waage, Johannes

AU - Wareham, Nick J.

AU - Weiss, Scott T.

AU - White, Wendy B.

AU - Wickman, Magnus

AU - Widén, Elisabeth

AU - Willemsen, Gonneke

AU - Williams, L. Keoki

AU - Wouters, Inge M.

AU - Yang, James J.

AU - Zhao, Jing Hua

AU - Moffatt, Miriam F.

AU - Ober, Carole

AU - Nicolae, Dan L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85039152884&partnerID=8YFLogxK

U2 - 10.1038/s41588-017-0014-7

DO - 10.1038/s41588-017-0014-7

M3 - Article

C2 - 29273806

AN - SCOPUS:85039152884

VL - 50

SP - 42

EP - 50

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 1

ER -

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

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