Kristin M Burkart1, Tamar Sofer2,3, Stephanie J London4, Ani Manichaikul5, Fernando P Hartwig6, Qi Yan7, María Soler Artigas8, Lydiana Avila9, Wei Chen7, Sonia Davis Thomas10, Alejandro A Diaz11, Ian P Hall12, Bernardo L Horta6, Robert C Kaplan13, Cathy C Laurie3, Ana M Menezes6, Jean V Morrison14, Elizabeth C Oelsner1, Deepa Rastogi15, Stephen S Rich5, Manuel Soto-Quiros7, Adrienne M Stilp3, Martin D Tobin8,16, Louise V Wain8,16, Juan C Celedón7, R Graham Barr1,17. 1. 1 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York. 2. 2 Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 3. 3 Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington. 4. 4 Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina. 5. 5 Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia. 6. 6 Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. 7. 7 Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania. 8. 8 Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom. 9. 9 Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica. 10. 10 Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina. 11. 11 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 12. 12 Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom. 13. 13 Department of Epidemiology and Population Health and. 14. 14 Department of Human Genetics and Statistics, University of Chicago, Chicago, Illinois. 15. 15 Department of Pediatrics, Albert Einstein College of Medicine, New York, New York. 16. 16 National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom; and. 17. 17 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
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 FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10-9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with 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. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos 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.
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 FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10-9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with 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. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos 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.
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