Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

Harriet Corvol; Scott M. Blackman; Pierre Yves Boëlle; Paul J. Gallins; Rhonda G. Pace; Jaclyn R. Stonebraker; Frank J. Accurso; Annick Clement; Joseph M. Collaco; Hong Dang; Anthony T. Dang; Arianna Franca; Jiafen Gong; Loic Guillot; Katherine Keenan; Weili Li; Fan Lin; Michael V. Patrone; Karen S. Raraigh; Lei Sun; Yi Hui Zhou; Wanda K. Wanda; Marci K. Sontag; Hara Levy; Peter R. Durie; Johanna M. Rommens; Mitchell L. Drumm; Fred A. Wright; Lisa J. Strug; Garry R. Cutting; Michael R. Knowles

doi:10.1038/ncomms9382

Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

Harriet Corvol, Scott M. Blackman, Pierre Yves Boëlle, Paul J. Gallins, Rhonda G. Pace, Jaclyn R. Stonebraker, Frank J. Accurso, Annick Clement, Joseph M. Collaco, Hong Dang, Anthony T. Dang, Arianna Franca, Jiafen Gong, Loic Guillot, Katherine Keenan, Weili Li, Fan Lin, Michael V. Patrone, Karen S. Raraigh, Lei SunYi Hui Zhou, Wanda K. Wanda, Marci K. Sontag, Hara Levy, Peter R. Durie, Johanna M. Rommens, Mitchell L. Drumm, Fred A. Wright, Lisa J. Strug, Garry R. Cutting, Michael R. Knowles

School of Medicine

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

156 Scopus citations

Abstract

The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10^-11), chr5p15.3 (SLC9A3; P=6.8 × 10^-12), chr6p21.3 (HLA Class II; P=1.2 × 10^-8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10^-9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10^-10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.

Original language	English (US)
Article number	8382
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9382
State	Published - Sep 29 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/ncomms9382

Cite this

Corvol, H., Blackman, S. M., Boëlle, P. Y., Gallins, P. J., Pace, R. G., Stonebraker, J. R., Accurso, F. J., Clement, A., Collaco, J. M., Dang, H., Dang, A. T., Franca, A., Gong, J., Guillot, L., Keenan, K., Li, W., Lin, F., Patrone, M. V., Raraigh, K. S., ... Knowles, M. R. (2015). Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nature communications, 6, Article 8382. https://doi.org/10.1038/ncomms9382

Corvol, H, Blackman, SM, Boëlle, PY, Gallins, PJ, Pace, RG, Stonebraker, JR, Accurso, FJ, Clement, A, Collaco, JM, Dang, H, Dang, AT, Franca, A, Gong, J, Guillot, L, Keenan, K, Li, W, Lin, F, Patrone, MV, Raraigh, KS, Sun, L, Zhou, YH, Wanda, WK, Sontag, MK, Levy, H, Durie, PR, Rommens, JM, Drumm, ML, Wright, FA, Strug, LJ, Cutting, GR & Knowles, MR 2015, 'Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis', Nature communications, vol. 6, 8382. https://doi.org/10.1038/ncomms9382

@article{58a4c59acce44a86bd1280f2b5546ff6,

title = "Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis",

abstract = "The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10-11), chr5p15.3 (SLC9A3; P=6.8 × 10-12), chr6p21.3 (HLA Class II; P=1.2 × 10-8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10-9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10-10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.",

author = "Harriet Corvol and Blackman, {Scott M.} and Bo{\"e}lle, {Pierre Yves} and Gallins, {Paul J.} and Pace, {Rhonda G.} and Stonebraker, {Jaclyn R.} and Accurso, {Frank J.} and Annick Clement and Collaco, {Joseph M.} and Hong Dang and Dang, {Anthony T.} and Arianna Franca and Jiafen Gong and Loic Guillot and Katherine Keenan and Weili Li and Fan Lin and Patrone, {Michael V.} and Raraigh, {Karen S.} and Lei Sun and Zhou, {Yi Hui} and Wanda, {Wanda K.} and Sontag, {Marci K.} and Hara Levy and Durie, {Peter R.} and Rommens, {Johanna M.} and Drumm, {Mitchell L.} and Wright, {Fred A.} and Strug, {Lisa J.} and Cutting, {Garry R.} and Knowles, {Michael R.}",

year = "2015",

month = sep,

day = "29",

doi = "10.1038/ncomms9382",

language = "English (US)",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

AU - Corvol, Harriet

AU - Blackman, Scott M.

AU - Boëlle, Pierre Yves

AU - Gallins, Paul J.

AU - Pace, Rhonda G.

AU - Stonebraker, Jaclyn R.

AU - Accurso, Frank J.

AU - Clement, Annick

AU - Collaco, Joseph M.

AU - Dang, Hong

AU - Dang, Anthony T.

AU - Franca, Arianna

AU - Gong, Jiafen

AU - Guillot, Loic

AU - Keenan, Katherine

AU - Li, Weili

AU - Lin, Fan

AU - Patrone, Michael V.

AU - Raraigh, Karen S.

AU - Sun, Lei

AU - Zhou, Yi Hui

AU - Wanda, Wanda K.

AU - Sontag, Marci K.

AU - Levy, Hara

AU - Durie, Peter R.

AU - Rommens, Johanna M.

AU - Drumm, Mitchell L.

AU - Wright, Fred A.

AU - Strug, Lisa J.

AU - Cutting, Garry R.

AU - Knowles, Michael R.

PY - 2015/9/29

Y1 - 2015/9/29

N2 - The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10-11), chr5p15.3 (SLC9A3; P=6.8 × 10-12), chr6p21.3 (HLA Class II; P=1.2 × 10-8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10-9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10-10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.

AB - The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10-11), chr5p15.3 (SLC9A3; P=6.8 × 10-12), chr6p21.3 (HLA Class II; P=1.2 × 10-8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10-9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10-10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.

UR - http://www.scopus.com/inward/record.url?scp=84942880568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942880568&partnerID=8YFLogxK

U2 - 10.1038/ncomms9382

DO - 10.1038/ncomms9382

M3 - Article

C2 - 26417704

AN - SCOPUS:84942880568

SN - 2041-1723

VL - 6

JO - Nature communications

JF - Nature communications

M1 - 8382

ER -

Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this