Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

J.B. Wilk; N.R.G. Shrine; L.R. Loehr; J.H. Zhao; A. Manichaikul; L.M. Lopez; A.V. Smith; S.R. Heckbert; J. Smolonska; W. Tang; D.W. Loth; I. Curjuric; Jennie Hui; M.H. Cho; J.C. Latourelle; A.P. Henry; M. Aldrich; P. Bakke; T.H. Beaty; A.R. Bentley; I.B. Borecki; G.G. Brusselle; K.M. Burkart; T.-H. Chen; D. Couper; J.D. Crapo; G. Davies; J. Dupuis; N. Franceschini; A. Gulsvik; D.B. Hancock; T.B. Harris; A. Hofman; M. Imboden; Alan James; K.-T. Khaw; L. Lahousse; L.J. Launer; A. Litonjua; Y. Liu; K.K. Lohman; D.A. Lomas; T. Lumley; K.D. Marciante; W.L. Mcardle; B. Meibohm; A.C. Morrison; Arthur Musk; R.H. Myers; K.E. North; D.S. Postma; B.M. Psaty; S.S. Rich; F. Rivadeneira; T. Rochat; J.I. Rotter; M. Soler Artigas; J.M. Starr; A.G. Uitterlinden; N.J. Wareham; C. Wijmenga; P. Zanen; M.A. Province; E.K. Silverman; I.J. Deary; L.J. Palmer; P.A. Cassano; V. Gudnason; R.G. Barr; R.J.F. Loos; D.P. Strachan; S.J. London; H.M. Boezen; N. Probst-Hensch; S.A. Gharib; I.P. Hall; G.T. O'Connor; M.D. Tobin; B.H. Stricker

doi:10.1164/rccm.201202-0366OC

Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

J.B. Wilk, N.R.G. Shrine, L.R. Loehr, J.H. Zhao, A. Manichaikul, L.M. Lopez, A.V. Smith, S.R. Heckbert, J. Smolonska, W. Tang, D.W. Loth, I. Curjuric, Jennie Hui, M.H. Cho, J.C. Latourelle, A.P. Henry, M. Aldrich, P. Bakke, T.H. Beaty, A.R. BentleyI.B. Borecki, G.G. Brusselle, K.M. Burkart, T.-H. Chen, D. Couper, J.D. Crapo, G. Davies, J. Dupuis, N. Franceschini, A. Gulsvik, D.B. Hancock, T.B. Harris, A. Hofman, M. Imboden, Alan James, K.-T. Khaw, L. Lahousse, L.J. Launer, A. Litonjua, Y. Liu, K.K. Lohman, D.A. Lomas, T. Lumley, K.D. Marciante, W.L. Mcardle, B. Meibohm, A.C. Morrison, Arthur Musk, R.H. Myers, K.E. North, D.S. Postma, B.M. Psaty, S.S. Rich, F. Rivadeneira, T. Rochat, J.I. Rotter, M. Soler Artigas, J.M. Starr, A.G. Uitterlinden, N.J. Wareham, C. Wijmenga, P. Zanen, M.A. Province, E.K. Silverman, I.J. Deary, L.J. Palmer, P.A. Cassano, V. Gudnason, R.G. Barr, R.J.F. Loos, D.P. Strachan, S.J. London, H.M. Boezen, N. Probst-Hensch, S.A. Gharib, I.P. Hall, G.T. O'Connor, M.D. Tobin, B.H. Stricker

School of Population and Global Health

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

155 Citations (Scopus)

Abstract

[Truncated abstract] Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers....Copyright © 2012 by the American Thoracic Society

Original language	English
Pages (from-to)	622-632
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	186
Issue number	7
DOIs	https://doi.org/10.1164/rccm.201202-0366OC
Publication status	Published - 2012

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Wilk, J. B., Shrine, N. R. G., Loehr, L. R., Zhao, J. H., Manichaikul, A., Lopez, L. M., Smith, A. V., Heckbert, S. R., Smolonska, J., Tang, W., Loth, D. W., Curjuric, I., Hui, J., Cho, M. H., Latourelle, J. C., Henry, A. P., Aldrich, M., Bakke, P., Beaty, T. H., ... Stricker, B. H. (2012). Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. American Journal of Respiratory and Critical Care Medicine, 186(7), 622-632. https://doi.org/10.1164/rccm.201202-0366OC

@article{835fe468bb2f4f5b8c201688b2df2156,

title = "Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction",

abstract = "[Truncated abstract] Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers....Copyright {\textcopyright} 2012 by the American Thoracic Society",

author = "J.B. Wilk and N.R.G. Shrine and L.R. Loehr and J.H. Zhao and A. Manichaikul and L.M. Lopez and A.V. Smith and S.R. Heckbert and J. Smolonska and W. Tang and D.W. Loth and I. Curjuric and Jennie Hui and M.H. Cho and J.C. Latourelle and A.P. Henry and M. Aldrich and P. Bakke and T.H. Beaty and A.R. Bentley and I.B. Borecki and G.G. Brusselle and K.M. Burkart and T.-H. Chen and D. Couper and J.D. Crapo and G. Davies and J. Dupuis and N. Franceschini and A. Gulsvik and D.B. Hancock and T.B. Harris and A. Hofman and M. Imboden and Alan James and K.-T. Khaw and L. Lahousse and L.J. Launer and A. Litonjua and Y. Liu and K.K. Lohman and D.A. Lomas and T. Lumley and K.D. Marciante and W.L. Mcardle and B. Meibohm and A.C. Morrison and Arthur Musk and R.H. Myers and K.E. North and D.S. Postma and B.M. Psaty and S.S. Rich and F. Rivadeneira and T. Rochat and J.I. Rotter and {Soler Artigas}, M. and J.M. Starr and A.G. Uitterlinden and N.J. Wareham and C. Wijmenga and P. Zanen and M.A. Province and E.K. Silverman and I.J. Deary and L.J. Palmer and P.A. Cassano and V. Gudnason and R.G. Barr and R.J.F. Loos and D.P. Strachan and S.J. London and H.M. Boezen and N. Probst-Hensch and S.A. Gharib and I.P. Hall and G.T. O'Connor and M.D. Tobin and B.H. Stricker",

year = "2012",

doi = "10.1164/rccm.201202-0366OC",

language = "English",

volume = "186",

pages = "622--632",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "7",

}

Wilk, JB, Shrine, NRG, Loehr, LR, Zhao, JH, Manichaikul, A, Lopez, LM, Smith, AV, Heckbert, SR, Smolonska, J, Tang, W, Loth, DW, Curjuric, I, Hui, J, Cho, MH, Latourelle, JC, Henry, AP, Aldrich, M, Bakke, P, Beaty, TH, Bentley, AR, Borecki, IB, Brusselle, GG, Burkart, KM, Chen, T-H, Couper, D, Crapo, JD, Davies, G, Dupuis, J, Franceschini, N, Gulsvik, A, Hancock, DB, Harris, TB, Hofman, A, Imboden, M, James, A, Khaw, K-T, Lahousse, L, Launer, LJ, Litonjua, A, Liu, Y, Lohman, KK, Lomas, DA, Lumley, T, Marciante, KD, Mcardle, WL, Meibohm, B, Morrison, AC, Musk, A, Myers, RH, North, KE, Postma, DS, Psaty, BM, Rich, SS, Rivadeneira, F, Rochat, T, Rotter, JI, Soler Artigas, M, Starr, JM, Uitterlinden, AG, Wareham, NJ, Wijmenga, C, Zanen, P, Province, MA, Silverman, EK, Deary, IJ, Palmer, LJ, Cassano, PA, Gudnason, V, Barr, RG, Loos, RJF, Strachan, DP, London, SJ, Boezen, HM, Probst-Hensch, N, Gharib, SA, Hall, IP, O'Connor, GT, Tobin, MD & Stricker, BH 2012, 'Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction', American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 7, pp. 622-632. https://doi.org/10.1164/rccm.201202-0366OC

TY - JOUR

T1 - Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

AU - Wilk, J.B.

AU - Shrine, N.R.G.

AU - Loehr, L.R.

AU - Zhao, J.H.

AU - Manichaikul, A.

AU - Lopez, L.M.

AU - Smith, A.V.

AU - Heckbert, S.R.

AU - Smolonska, J.

AU - Tang, W.

AU - Loth, D.W.

AU - Curjuric, I.

AU - Hui, Jennie

AU - Cho, M.H.

AU - Latourelle, J.C.

AU - Henry, A.P.

AU - Aldrich, M.

AU - Bakke, P.

AU - Beaty, T.H.

AU - Bentley, A.R.

AU - Borecki, I.B.

AU - Brusselle, G.G.

AU - Burkart, K.M.

AU - Chen, T.-H.

AU - Couper, D.

AU - Crapo, J.D.

AU - Davies, G.

AU - Dupuis, J.

AU - Franceschini, N.

AU - Gulsvik, A.

AU - Hancock, D.B.

AU - Harris, T.B.

AU - Hofman, A.

AU - Imboden, M.

AU - James, Alan

AU - Khaw, K.-T.

AU - Lahousse, L.

AU - Launer, L.J.

AU - Litonjua, A.

AU - Liu, Y.

AU - Lohman, K.K.

AU - Lomas, D.A.

AU - Lumley, T.

AU - Marciante, K.D.

AU - Mcardle, W.L.

AU - Meibohm, B.

AU - Morrison, A.C.

AU - Musk, Arthur

AU - Myers, R.H.

AU - North, K.E.

AU - Postma, D.S.

AU - Psaty, B.M.

AU - Rich, S.S.

AU - Rivadeneira, F.

AU - Rochat, T.

AU - Rotter, J.I.

AU - Soler Artigas, M.

AU - Starr, J.M.

AU - Uitterlinden, A.G.

AU - Wareham, N.J.

AU - Wijmenga, C.

AU - Zanen, P.

AU - Province, M.A.

AU - Silverman, E.K.

AU - Deary, I.J.

AU - Palmer, L.J.

AU - Cassano, P.A.

AU - Gudnason, V.

AU - Barr, R.G.

AU - Loos, R.J.F.

AU - Strachan, D.P.

AU - London, S.J.

AU - Boezen, H.M.

AU - Probst-Hensch, N.

AU - Gharib, S.A.

AU - Hall, I.P.

AU - O'Connor, G.T.

AU - Tobin, M.D.

AU - Stricker, B.H.

PY - 2012

Y1 - 2012

N2 - [Truncated abstract] Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers....Copyright © 2012 by the American Thoracic Society

AB - [Truncated abstract] Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers....Copyright © 2012 by the American Thoracic Society

U2 - 10.1164/rccm.201202-0366OC

DO - 10.1164/rccm.201202-0366OC

M3 - Article

C2 - 22837378

SN - 1073-449X

VL - 186

SP - 622

EP - 632

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 7

ER -

Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

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