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BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.

A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.

Collaborators (250)

Crapo J, Silverman E, Make B, Regan E, Lantz R, Stepp L, Melanson S, Beaty T, Klanderman B, Laird N, Lange C, Cho M, Santorico S, Hokanson J, DeMeo D, Hansel N, Hersh C, Castaldi P, McDonald ML, Zhou J, Mattheissen M, Wan E, Hardin M, Hetmanski J, Parker M, Murray T, Lynch D, Schroeder J, Newell J Jr, Reilly J, Coxson H, Judy P, Hoffman E, Washko G, San Jose Estepar R, Ross J, Al Qaisi M, Zach J, Kluiber A, Sieren J, Mann T, Richert D, McKenzie A, Akhavan J, Stinson D, Jensen R, Farzadegan H, Meyerer S, Chandan S, Bragan S, Everett D, Williams A, Wilson C, Forssen A, Powell A, Piccoli J, Hokanson J, Sontag M, Black-Shinn J, Kinney G, Lutz S, Curtis J, Kazerooni E, Hanania N, Alapat P, Bandi V, Guntupalli K, Guy E, Mallampalli A, Trinh C, Atik M, Al-Azzawi H, Willis M, Pinero S, Fahr L, Nachiappan A, Bray C, Frigini LA, Farinas C, Katz D, Freytes J, Marciel AM, DeMeo D, Hersh C, Washko G, Jacobson F, Hatabu H, Clarke P, Gill R, Hunsaker A, Trotman-Dickenson B, Madan R, Barr RG, Thomashow B, Austin J, D'Souza B, MacIntyre N Jr, Washington L, McAdams HP, Rosiello R, Bresnahan T, Bradley J, Kuong S, Meller S, Roland S, McEvoy C, Tashjian J, Wise R, Hansel N, Brown R, Diette G, Horton K, Casaburi R, Porszasz J, Fischer H, Budoff M, Rambod M, Sharafkhaneh A, Trinh C, Kamal H, Darvishi R, Willis M, Pinero S, Fahr L, Nachiappan A, Bray C, Frigini LA, Farinas C, Katz D, Freytes J, Marciel AM, Niewoehner D, Anderson Q, Rice K, Caine A, Foreman M, Westney G, Berkowitz E, Bowler R, Lynch D, Schroeder J, Hale V, Armstrong J 2nd, Dyer D, Chung J, Cox C, Criner G, Kim V, Marchetti N, Satti A, Mamary AJ, Steiner R, Dass C, Cone L, Bailey W, Dransfield M, Wells M, Bhatt S, Nath H, Singh S, Ramsdell J, Friedman P, Cornellas A, Newell J Jr, van Beek EJ, Martinez F, Han M, Kazerooni E, Wendt C, Allen T, Sciurba F, Weissfeld J, Fuhrman C, Bon J, Hooper D, Anzueto A, Adams S, Orozco C, Ruiz M, Mumbower A, Kruger A, Restrepo C, Lane M, Ivanov Y, Kostov K, Bourbeau J, Fitzgerald M, Hernandez P, Killian K, Levy R, Maltais F, O'Donnell D, Krepelka J, Vestbo J, Wouters E, Quinn D, Bakke P, Kosnik M, Agusti A, Sauleda J, de Mallorca P, Feschenko Y, Gavrisyuk V, Yashina L, Monogarova N, Calverley P, Lomas D, MacNee W, Singh D, Wedzicha J, Anzueto A, Braman S, Casaburi R, Celli B, Giessel G, Gotfried M, Greenwald G, Hanania N, Mahler D, Make B, Rennard S, Rochester C, Scanlon P, Schuller D, Sciurba F, Sharafkhaneh A, Siler T, Silverman E, Wanner A, Wise R, ZuWallack R, Coxson H, Crim C, Edwards L, Lomas D, MacNee W, Silverman E, Tal Singer R, Vestbo J, Yates J, Agusti A, Calverley P, Celli B, Crim C, Miller B, MacNee W, Rennard S, Tal-Singer R, Wouters E, Yates J.

Author information

1
Department of Biostatistics, University of Colorado Anschutz Medical Campus, 13001 E. 17th Place, B119 Bldg. 500, W3128, Aurora, CO, 80045, USA. sharon.lutz@ucdenver.edu.
2
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. remhc@channing.harvard.edu.
3
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. kendra.young@ucdenver.edu.
4
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. craig.hersh@channing.harvard.edu.
5
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. repjc@channing.harvard.edu.
6
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. remrm@channing.harvard.edu.
7
Department of Medicine, National Jewish Health, Denver, CO, USA. regane@njhealth.org.
8
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. mm@hum-gen.au.dk.
9
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. redld@channing.harvard.edu.
10
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. mmparker1@gmail.com.
11
Morehouse School of Medicine, Atlanta, GA, USA. mforeman@msm.edu.
12
Department of Medicine, National Jewish Health, Denver, CO, USA. makeb@njhealth.org.
13
Division of Pulmonary, Allergy & Critical Care Medicine, LDS Hospital, Salt Lake City, UT, USA. ldrjens1@ihc.com.
14
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. casaburi@ucla.edu.
15
Wolfson Institute for Biomedical Research, University College London, London, UK. d.lomas@ucl.ac.uk.
16
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. spbhatt@uab.edu.
17
Department of Clinical Science, University of Bergen, Bergen, Norway. per.bakke@med.uib.no.
18
Department of Clinical Science, University of Bergen, Bergen, Norway. amund.gulsvik@med.uib.no.
19
Department of Medicine, National Jewish Health, Denver, CO, USA. crapoj@njc.org.
20
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. tbeaty@jhsph.edu.
21
Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. nanlaird@gmail.com.
22
Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. langech2007@gmail.com.
23
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. John.Hokanson@ucdenver.edu.
24
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ed.silverman@channing.harvard.edu.

Abstract

BACKGROUND:

Pulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532).

RESULTS:

Among NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10(-11)), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10(-10)); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 9 [DBH] (p-value = 9.69 × 10(-9)) and 19 [CYP2A6/7] (p-value = 3.49 × 10(-8)) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 4 [FAM13A] (p-value = 3.88 × 10(-12)), 11 [MMP3/12] (p-value = 3.29 × 10(-10)) and 14 [RIN3] (p-value = 5.64 × 10(-9)).

CONCLUSIONS:

In a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00292552 NCT00608764.

PMID:
26634245
PMCID:
PMC4668640
DOI:
10.1186/s12863-015-0299-4
[Indexed for MEDLINE]
Free PMC Article

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