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Cited by 170

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Open access
Wilk, Jemma B., Shrine, Nick R. G., Loehr, Laura R., Zhao, Jing Hua, Manichaikul, Ani, Lopez, Lorna M., Smith, Albert Vernon, Heckbert, Susan R., Smolonska, Joanna, Tang, Wenbo, Loth, Daan W., Curjuric, Ivan, Hui, Jennie, Cho, Michael H., Latourelle, Jeanne C., Henry, Amanda P., Aldrich, Melinda, Bakke, Per, Beaty, Terri H., Bentley, Amy R., Borecki, Ingrid B., Brusselle, Guy G., Burkart, Kristin M., Chen, Ting-hsu, Couper, David, Crapo, James D., Davies, Gail, Dupuis, Josée, Franceschini, Nora, Gulsvik, Amund, Hancock, Dana B., Harris, Tamara B., Hofman, Albert, Imboden, Medea, James, Alan L., Khaw, Kay-Tee, Lahousse, Lies, Launer, Lenore J., Litonjua, Augusto, Liu, Yongmei, Lohman, Kurt K., Lomas, David A., Lumley, Thomas, Marciante, Kristin D., McArdle, Wendy L., Meibohm, Bernd, Morrison, Alanna C., Musk, Arthur W., Myers, Richard H., North, Kari E., Postma, Dirkje S., Psaty, Bruce M., Rich, Stephen S., Rivadeneira, Fernando, Rochat, Thierry, Rotter, Jerome I., Artigas, María Soler, Starr, John M., Uitterlinden, André G., Wareham, Nicholas J., Wijmenga, Cisca, Zanen, Pieter, Province, Michael A., Silverman, Edwin K., Deary, Ian J., Palmer, Lyle J., Cassano, Patricia A., Gudnason, Vilmundur, Barr, R. Graham, Loos, Ruth J. F., Strachan, David P., London, Stephanie J., Boezen, H. Marike, Probst-Hensch, Nicole, Gharib, Sina A., Hall, Ian P., O’Connor, George T., Tobin, Martin D., Stricker, Bruno H.·2012·American Journal of Respiratory and Critical Care Medicine
DOI 10.1164/rccm.201202-0366oc
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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 FEV(1) and its ratio to FVC (FEV(1)/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. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis. CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.

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Metadata

Authors
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., Bentley, A. R., Borecki, I. B., Brusselle, G. G., Burkart, K. M., Chen, T.-H., Couper, D., Crapo, J. D., Davies, G., Dupuis, J., Franceschini, N., Gulsvik, A., Hancock, D. B., Harris, T. B., Hofman, A., Imboden, M., James, A. L., Khaw, K.-T., Lahousse, L., Launer, L. J., Litonjua, A., Liu, Y., Lohman, K. K., Lomas, D. A., Lumley, T., Marciante, K. D., McArdle, W. L., Meibohm, B., Morrison, A. C., Musk, A. W., Myers, R. H., North, K. E., Postma, D. S., Psaty, B. M., Rich, S. S., Rivadeneira, F., Rochat, T., Rotter, J. I., Artigas, M. S., Starr, J. M., Uitterlinden, A. G., Wareham, N. J., Wijmenga, C., Zanen, P., Province, M. A., Silverman, E. K., Deary, I. J., Palmer, L. J., Cassano, P. A., Gudnason, V., Barr, R. G., Loos, R. J. F., Strachan, D. P., London, S. J., Boezen, H. M., Probst-Hensch, N., Gharib, S. A., Hall, I. P., O’Connor, G. T., Tobin, M. D., & Stricker, B. H.
Venue
American Journal of Respiratory and Critical Care Medicine
Publisher
Oxford University Press (OUP)
Published
2012-10-01
Volume
186
Issue
7
Pages
622-632
ISSN
  • 1073-449X (ISSN-L)
  • 1535-4970
DOI
10.1164/rccm.201202-0366oc
OpenAlex
W2168850818
Cited by
170
References
7
FWCI
14.47
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction. https://app.cochat.ai/papers/10.1164/rccm.201202-0366oc
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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. https://doi.org/10.1164/rccm.201202-0366oc

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.