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Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos
journal contribution
posted on 2018-01-26, 16:48 authored by Kristin M. Burkart, Tamar Sofer, Stephanie J. London, Ani Manichaikul, Fernando P. Hartwig, Qi Yan, María Soler Artigas, Lydiana Avila, Wei Chen, Sonia Davis Thomas, Alejandro A. Diaz, Ian P. Hall, 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. Celedón, R. Graham BarrRationale: 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 to genetic etiologies of COPD.
Funding
HCHS/SOL: We thank the participants and staff of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) for their contributions to this study. The baseline examination of HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes, centers, and offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, and NIH Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Additional analysis support was provided by 1R01DK101855-01and13GRNT16490017. Genotyping efforts were supported by the NIH Department of Health and Human Services (HSN26220/20054C), National Center for Advancing Translational Science Clinical Translational Science Institute (UL1TR000124), and NIDDK Diabetes Research Center (DK063491). This manuscript has been reviewed by the HCHS/SOL Publications Committee for scientific content and consistency of data interpretation with previous HCHS/SOL publications. TS is supported by NHLBI 1R35HL135818. AAD is supported by K01HL118714 and the Brigham and Women’s Hospital Minority Faculty Career Development Award. SJL is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. RGB is supported by R01-HL077612 and R01-HL092081. COPD-Costa Rica, MESA Lung, 1982 Pelotas Birth
History
Citation
American Journal of Respiratory and Critical Care Medicine, 2018Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health SciencesVersion
- AM (Accepted Manuscript)
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American Journal of Respiratory and Critical Care MedicinePublisher
American Thoracic Societyissn
1073-449Xeissn
1535-4970Acceptance date
2018-01-20Copyright date
2018Available date
2018-03-28Publisher DOI
Publisher version
https://www.atsjournals.org/doi/abs/10.1164/rccm.201707-1493OCLanguage
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