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A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos

Burkart, Kristin M.; Sofer, Tamar; London, Stephanie J.; Manichaikul, Ani; Hartwig, Fernando P.; Yan, Qi; Artigas, Mar�a Soler; Avila, Lydiana; Chen, Wei; Thomas, Sonia Davis; Diaz, Alejandro A.; Hall, Ian P.; Horta, Bernardo L.; Kaplan, Robert C.; Laurie, Cathy C.; Menezes, Ana M.; Morrison, Jean V.; Oelsner, Elizabeth C.; Rastogi, Deepa; Rich, Stephen S.; Soto-Quiros, Manuel; Stilp, Adrienne M.; Tobin, Martin D.; Wain, Louise V.; Celedon, Juan C.; Barr, R. Graham

A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos Thumbnail


Authors

Kristin M. Burkart

Tamar Sofer

Stephanie J. London

Ani Manichaikul

Fernando P. Hartwig

Qi Yan

Mar�a Soler Artigas

Lydiana Avila

Wei Chen

Sonia Davis Thomas

Alejandro A. Diaz

IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine

Bernardo L. Horta

Robert C. Kaplan

Cathy C. Laurie

Ana M. Menezes

Jean V. Morrison

Elizabeth C. Oelsner

Deepa Rastogi

Stephen S. Rich

Manuel Soto-Quiros

Adrienne M. Stilp

Martin D. Tobin

Louise V. Wain

Juan C. Celedon

R. Graham Barr



Abstract

Rationale: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.
Objectives: Perform a GWAS of COPD-phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.
Methods: GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.
Measurements and Main Results: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for forced expiratory volume in one second (FEV1) in ZSWIM7 (rs4791658; p=4.99×10-9) replicated. A rare variant (MAF=0.002) in HAL (rs145174011) was associated with FEV1 to forced vital capacity (FEV1/FVC) (p=9.59×10-9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; p=1.92×10-8) approached statistical significance for replication in admixed populations of African ancestry and a novel SNP for COPD in PDZD2 (rs7709630; p=1.56×10-8) regionally replicated. Additionally, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in HCHS/SOL at the genome-wide significance level.
Conclusions: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing togenetic etiologies of COPD.

Citation

Burkart, K. M., Sofer, T., London, S. J., Manichaikul, A., Hartwig, F. P., Yan, Q., …Barr, R. G. (2018). A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos. American Journal of Respiratory and Critical Care Medicine, 198(2), 208-219. https://doi.org/10.1164/rccm.201707-1493OC

Journal Article Type Article
Acceptance Date Jan 30, 2018
Online Publication Date Feb 2, 2018
Publication Date Jul 15, 2018
Deposit Date Feb 13, 2018
Publicly Available Date Feb 13, 2018
Journal American Journal of Respiratory and Critical Care Medicine
Print ISSN 1073-449X
Electronic ISSN 1535-4970
Publisher American Thoracic Society
Peer Reviewed Peer Reviewed
Volume 198
Issue 2
Pages 208-219
DOI https://doi.org/10.1164/rccm.201707-1493OC
Keywords Hispanic/Latino, genome-wide association, single nucleotide polymorphisms, lung function, chronic obstructive pulmonary disease
Public URL https://nottingham-repository.worktribe.com/output/908355
Publisher URL https://www.atsjournals.org/doi/10.1164/rccm.201707-1493OC
Additional Information Copyright © 2018 by the American Thoracic Society
Contract Date Feb 13, 2018