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; 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

doi:10.1038/s41588-017-0014-7

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

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

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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 language	English
Pages (from-to)	42-53
Number of pages	12
Journal	Nature Genetics
Volume	50
Issue number	1
Early online date	22 Dec 2017
DOIs	https://doi.org/10.1038/s41588-017-0014-7
Publication status	Published - Jan 2018

Funding

Funders	Funder number
Medical Research Council	MC_UU_12015/1, MC_PC_13048, G9815508, G0401540, MR/K002449/2, MR/K002449/1, G0601361
National Heart, Lung, and Blood Institute	R01HL077612, RC2HL101651, U01HL130114
Horizon 2020 Framework Programme	733206, 648916
National Institute of Environmental Health Sciences	ZIAES043012, P30ES006694, ZIAES049019, P30ES009089
National Cancer Institute	P01CA196569

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Journal Article

Cohort Studies

Netherlands Twin Register (NTR)

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10.1038/s41588-017-0014-7

Multiancestry association study identifies new asthma risk loci that colocalize with immunecell enhancer marksFinal published version, 1.95 MBLicence: Article 25fa Dutch Copyright Act

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Demenais, F., Margaritte-Jeannin, P., Barnes, K. C., Cookson, W. O. C., Altmüller, J., Ang, W., Barr, R. G., Beaty, T. H., Becker, A. B., Beilby, J., Bisgaard, H., Bjornsdottir, U. S., Bleecker, E., Bønnelykke, K., Boomsma, D. I., Bouzigon, E., Brightling, C. E., Brossard, M., Brusselle, G. 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, 50(1), 42-53. https://doi.org/10.1038/s41588-017-0014-7

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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.",

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year = "2018",

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

language = "English",

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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

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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

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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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U2 - 10.1038/s41588-017-0014-7

DO - 10.1038/s41588-017-0014-7

M3 - Article

C2 - 29273806

SN - 1061-4036

VL - 50

SP - 42

EP - 53

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

Abstract

Funding

UN SDGs

Keywords

Cohort Studies

Access to Document

Persistent URL (handle)

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