Genome-Wide Study of Percent Emphysema on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study

Details

• Personal Author:
  Austin JHM ; Barr RG ; Baumhauer H ; Beaty TH ; Boezen HM ; Brantly ML ; Budoff M ; Carr JJ ; Cho MH ; Crapo JD ; Dupuis J ; Gao W ; Groen HJM ; Hinckley Stukovsky KD ; Hoffman EA ; Hokanson JE ; Kaufman JD ; Manichaikul A ; O'Connor GT ; Postma DS ; Pottinger T ; Powell CA ; Powell R ; Rabinowitz D ; Raffel LJ ; Rich SS ; Rouhani FN ; Silverman EK ; Smith BM ; Smolonska J ; Wanner A ; Washko GR ; Wijmenga C ; Zanen P
• Description:
  Rationale: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. Objectives: To 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. Methods: We 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 Results: Among 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 a-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 a-linked mannose. Among African Americans, a locus near a third a-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10-6; MAF, 13.3%) was associated with percent emphysema. Conclusions: Our 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 a-mannosidase may influence risk of emphysema. [Description provided by NIOSH]
• Subjects:
  Air Pollution Cohort Studies Environmental Exposure Environmental Pollution Genetics Lung Occupational Health Race Factors Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Air Pollution Author Keywords: Emphysema Cohort Studies Cohort Study Computed Tomography Environmental Pollution Genetic Association Genetic Testing Lung Function Multiethnic Racial Factors Respiratory Diseases Risk Factors

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Colorado ; Florida ; Iowa ; Massachusetts ; New York ; North Carolina ; OSHA Region 1 ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 7 ; OSHA Region 8 ; OSHA Region 9 ; Virginia ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  408-418
• Volume:
  189
• Issue:
  4
• NIOSHTIC Number:
  nn:20055126
• Citation:
  Am J Respir Crit Care Med 2014 Feb; 189(4):408-418
• Contact Point Address:
  R. Graham Barr, M.D., Dr.P.H., Columbia University Medical Center, 630 West 168th Street, PH 9 East, Room 105, New York, NY 10032
• Email:
  rgb9@columbia.edu
• Federal Fiscal Year:
  2014
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d1e99ac82997d0e9691673344c461ca3a22bd38ececae3b95e3a6d0c9355e69619af1e6b67ad1e50360ca6e536f03e17318a637f3dc931c5eda732ae610f5410
• Download URL:
  https://stacks.cdc.gov/view/cdc/217493/cdc_217493_DS1.pdf
• File Type:
  [PDF - 1.15 MB ]