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. M. 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 G. Burchard; Kristin M Burkart; Andrew Bush; Moira Chan-Yeung; Kian Fan Chung; Alexessander Da Silva 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; Raquel Granell; Penelope E Graves; Dick Heederik; Inge M Wouters; 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. M. 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 G. BurchardKristin M Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Da Silva 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, Raquel Granell, Penelope E Graves, Dick Heederik, Inge M Wouters, Australian Asthma Genetics Consortium (AAGC) collaborators

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Pages (from-to)	42-53
Number of pages	12
Journal	Nature Genetics
Volume	50
Issue number	1
DOIs	https://doi.org/10.1038/s41588-017-0014-7
Publication status	Published - Jan 2018

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Demenais, F., Margaritte-Jeannin, P., Barnes, K. C., Cookson, W. O. C. M., 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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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 = "Florence Demenais and Patricia Margaritte-Jeannin and Barnes, {Kathleen C} and Cookson, {William O. C. M.} 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 Burchard, {Esteban G.} and Burkart, {Kristin M} and Andrew Bush and Moira Chan-Yeung and Chung, {Kian Fan} and {Da Silva 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 Dick Heederik and Wouters, {Inge M} and {Australian Asthma Genetics Consortium (AAGC) collaborators}",

year = "2018",

month = jan,

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

language = "English",

volume = "50",

pages = "42--53",

journal = "Nature Genetics",

issn = "1061-4036",

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Demenais, F, Margaritte-Jeannin, P, Barnes, KC, Cookson, WOCM, 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, EG, Burkart, KM, Bush, A, Chan-Yeung, M, Chung, KF, Da Silva 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, Granell, R, Graves, PE, Heederik, D , Wouters, IM & 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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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. M.

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 G.

AU - Burkart, Kristin M

AU - Bush, Andrew

AU - Chan-Yeung, Moira

AU - Chung, Kian Fan

AU - Da Silva 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 - Heederik, Dick

AU - Wouters, Inge M

AU - Australian Asthma Genetics Consortium (AAGC) collaborators

PY - 2018/1

Y1 - 2018/1

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.

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

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