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 Burchard & 31 others 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, Susan R Heckbert, Jouke Hottenga, Hamdi Mbarek, Gonneke Willemsen, Australian Asthma Genetics Consortium (AAGC) collaborators

Research output: Contribution to JournalArticleAcademicpeer-review

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
DOIs
Publication statusPublished - Jan 2018

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Asthma
Seasonal Allergic Rhinitis
Genome-Wide Association Study
Autoimmune Diseases
Meta-Analysis
Comorbidity
Population

Keywords

  • Journal Article

Cite this

Demenais, F., Margaritte-Jeannin, P., Barnes, K. C., Cookson, W. O. C., Altmüller, J., Ang, W., ... Australian Asthma Genetics Consortium (AAGC) collaborators (2018). Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nature Genetics, 50(1), 42-53. https://doi.org/10.1038/s41588-017-0014-7
Demenais, Florence ; Margaritte-Jeannin, Patricia ; Barnes, Kathleen C ; Cookson, William O C ; Altmüller, Janine ; Ang, Wei ; Barr, R Graham ; Beaty, Terri H ; Becker, Allan B ; Beilby, John ; Bisgaard, Hans ; Bjornsdottir, Unnur Steina ; Bleecker, Eugene ; Bønnelykke, Klaus ; Boomsma, Dorret I ; Bouzigon, Emmanuelle ; Brightling, Christopher E ; Brossard, Myriam ; Brusselle, Guy G ; Burchard, Esteban ; Burkart, Kristin M ; Bush, Andrew ; Chan-Yeung, Moira ; Chung, Kian Fan ; Couto Alves, Alexessander ; Curtin, John A ; Custovic, Adnan ; Daley, Denise ; de Jongste, Johan C ; Del-Rio-Navarro, Blanca E ; Donohue, Kathleen M ; Duijts, Liesbeth ; Eng, Celeste ; Eriksson, Johan G ; Farrall, Martin ; Fedorova, Yuliya ; Feenstra, Bjarke ; Ferreira, Manuel A ; Freidin, Maxim B ; Gajdos, Zofia ; Gauderman, Jim ; Gehring, Ulrike ; Geller, Frank ; Genuneit, Jon ; Gharib, Sina A ; Gilliland, Frank ; Heckbert, Susan R ; Hottenga, Jouke ; Mbarek, Hamdi ; Willemsen, Gonneke ; Australian Asthma Genetics Consortium (AAGC) collaborators. / Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. In: Nature Genetics. 2018 ; Vol. 50, No. 1. pp. 42-53.
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Demenais, F, Margaritte-Jeannin, P, Barnes, KC, Cookson, WOC, Altmüller, J, Ang, W, Barr, RG, Beaty, TH, Becker, AB, Beilby, J, Bisgaard, H, Bjornsdottir, US, Bleecker, E, Bønnelykke, K, Boomsma, DI, Bouzigon, E, Brightling, CE, Brossard, M, Brusselle, GG, Burchard, E, Burkart, KM, Bush, A, Chan-Yeung, M, Chung, KF, Couto Alves, A, Curtin, JA, Custovic, A, Daley, D, de Jongste, JC, Del-Rio-Navarro, BE, Donohue, KM, Duijts, L, Eng, C, Eriksson, JG, Farrall, M, Fedorova, Y, Feenstra, B, Ferreira, MA, Freidin, MB, Gajdos, Z, Gauderman, J, Gehring, U, Geller, F, Genuneit, J, Gharib, SA, Gilliland, F, Heckbert, SR, Hottenga, J, Mbarek, H, Willemsen, G & Australian Asthma Genetics Consortium (AAGC) collaborators 2018, 'Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks' Nature Genetics, vol. 50, no. 1, pp. 42-53. https://doi.org/10.1038/s41588-017-0014-7

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. / Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C; Cookson, William O C; Altmüller, Janine; Ang, Wei; Barr, R Graham; Beaty, Terri H; Becker, Allan B; Beilby, John; Bisgaard, Hans; Bjornsdottir, Unnur Steina; Bleecker, Eugene; Bønnelykke, Klaus; Boomsma, Dorret I; Bouzigon, Emmanuelle; Brightling, Christopher E; Brossard, Myriam; Brusselle, Guy G; Burchard, Esteban; Burkart, Kristin M; Bush, Andrew; Chan-Yeung, Moira; Chung, Kian Fan; Couto Alves, Alexessander; Curtin, John A; Custovic, Adnan; Daley, Denise; de Jongste, Johan C; Del-Rio-Navarro, Blanca E; Donohue, Kathleen M; Duijts, Liesbeth; Eng, Celeste; Eriksson, Johan G; Farrall, Martin; Fedorova, Yuliya; Feenstra, Bjarke; Ferreira, Manuel A; Freidin, Maxim B; Gajdos, Zofia; Gauderman, Jim; Gehring, Ulrike; Geller, Frank; Genuneit, Jon; Gharib, Sina A; Gilliland, Frank; Heckbert, Susan R; Hottenga, Jouke; Mbarek, Hamdi; Willemsen, Gonneke; Australian Asthma Genetics Consortium (AAGC) collaborators.

In: Nature Genetics, Vol. 50, No. 1, 01.2018, p. 42-53.

Research output: Contribution to JournalArticleAcademicpeer-review

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

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 - Heckbert, Susan R

AU - Hottenga, Jouke

AU - Mbarek, Hamdi

AU - Willemsen, Gonneke

AU - Australian Asthma Genetics Consortium (AAGC) collaborators

PY - 2018/1

Y1 - 2018/1

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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.

KW - Journal Article

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DO - 10.1038/s41588-017-0014-7

M3 - Article

VL - 50

SP - 42

EP - 53

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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