Genome-wide study of percent emphysema on computed tomography in the general population
| Autor: | James D. Crapo, Adam Wanner, Matthew J. Budoff, Mark L. Brantly, Rhea E. Powell, Eric A. Hoffman, J. Jeffrey Carr, Harry J.M. Groen, Michael H. Cho, Heather Baumhauer, Dirkje S. Postma, Pieter Zanen, Wei Gao, John E. Hokanson, H. Marike Boezen, Leslie J. Raffel, Terri H. Beaty, Edwin K. Silverman, George R. Washko, George T. O'Connor, Joel D. Kaufman, Tess D. Pottinger, Joanna Smolonska, Cisca Wijmenga, Charles A. Powell, John H. M. Austin, Josée Dupuis, Daniel Rabinowitz, Ani Manichaikul, R. Graham Barr, Karen Hinckley Stukovsky, Benjamin M. Smith, Stephen S. Rich, Farshid N. Rouhani |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology Genotyping Techniques genetic association Respiratory System Genome-wide association study VARIANTS Cardiovascular Critical Care and Intensive Care Medicine Medical and Health Sciences AIR-FLOW OBSTRUCTION 80 and over HOMOZYGOUS DELETIONS 2.1 Biological and endogenous factors Aetiology Tomography Lung Aged 80 and over education.field_of_study COPD Single Nucleotide Middle Aged respiratory system X-Ray Computed ALPHA1-ANTITRYPSIN DEFICIENCY medicine.anatomical_structure emphysema Pulmonary Emphysema Cohort multiethnic Female SMOKING RNA Helicases Cohort study Genetic Markers Pulmonary and Respiratory Medicine medicine.medical_specialty Chronic Obstructive Pulmonary Disease Population Nerve Tissue Proteins N-Acetylglucosaminyltransferases Polymorphism Single Nucleotide OBSTRUCTIVE PULMONARY-DISEASE BREAST snRNP Core Proteins alpha-Mannosidase Clinical Research Internal medicine Mannosidases Genetics medicine cohort study Humans MESA Polymorphism education Aged Genetic association Emphysema SnRNP Core Proteins business.industry Human Genome computed tomography Atherosclerosis medicine.disease United States respiratory tract diseases Thiolester Hydrolases Tomography X-Ray Computed business CARDIAC CT Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine, 189(4), 408-418. AMER THORACIC SOC American journal of respiratory and critical care medicine, vol 189, iss 4 |
| ISSN: | 1073-449X |
| Popis: | RationalePulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.ObjectivesTo complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States.MethodsWe determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity.Measurements and main resultsAmong 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema.ConclusionsOur results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema. |
| Databáze: | OpenAIRE |
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