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

Ani Manichaikul; Eric A Hoffman; Joanna Smolonska; Wei Gao; Michael H Cho; Heather Baumhauer; Matthew Budoff; John H. M Austin; George R Washko; J. Jeffrey Carr; Joel D Kaufman; Tess Pottinger; Charles A Powell; Cisca Wijmenga; Pieter Zanen; Harry J. M Groen; Dirkje S Postma; Adam Wanner; Farshid N Rouhani; Mark L Brantly; Rhea Powell; Benjamin M Smith; Dan Rabinowitz; Leslie J Raffel; Karen D Hinckley Stukovsky; James D Crapo; Terri H Beaty; John E Hokanson; Edwin K Silverman; Josée Dupuis; George T O’Connor; H. Marike Boezen; Stephen S Rich; R. Graham Barr

doi:10.1164/rccm.201306-1061OC

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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

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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

Ani Manichaikul, Eric A Hoffman, Joanna Smolonska, Wei Gao, Michael H Cho, Heather Baumhauer, Matthew Budoff, John H. M Austin, George R Washko, J. Jeffrey Carr, …

American journal of respiratory and critical care medicine, Vol.189(4), pp.408-418

02/15/2014

DOI: 10.1164/rccm.201306-1061OC

PMCID: PMC3977717

PMID: 24383474

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Abstract

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 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. 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 α-mannosidase may influence risk of emphysema.

Computed Tomography

genetic association

cohort study

multiethnic

Original

emphysema

Details

Title: Subtitle: 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
Creators: Ani Manichaikul - Center for Public Health Genomics, and
Eric A Hoffman - Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Joanna Smolonska - Department of Epidemiology
Wei Gao - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
Michael H Cho - Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, and
Heather Baumhauer - Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Matthew Budoff - Division of Cardiology, Los Angeles Biomedical Research Institute, Torrance, California
John H. M Austin - Department of Radiology, Columbia University Medical Center, New York, New York
George R Washko - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts
J. Jeffrey Carr - Department of Radiology, Wake Forest University, Winston-Salem, North Carolina
Joel D Kaufman - Department of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, and
Tess Pottinger - Department of Medicine, College of Physicians and Surgeons
Charles A Powell - Department of Medicine, Mount Sinai Hospital, New York, New York
Cisca Wijmenga - Department of Genetics
Pieter Zanen - Department of Pulmonology, University Medical Center Utrecht, Utrecht, The Netherlands
Harry J. M Groen - Department of Pulmonology, and
Dirkje S Postma - Department of Pulmonology, and
Adam Wanner - Division of Pulmonary and Critical Care Medicine, University of Miami Miller School of Medicine, Miami, Florida
Farshid N Rouhani - Division of Pulmonary Critical Care and Sleep Medicine, College of Medicine, University of Florida, Gainesville, Florida
Mark L Brantly - Division of Pulmonary Critical Care and Sleep Medicine, College of Medicine, University of Florida, Gainesville, Florida
Rhea Powell - Department of Medicine, College of Physicians and Surgeons
Benjamin M Smith - Department of Medicine, College of Physicians and Surgeons
Dan Rabinowitz - Department of Statistics, and
Leslie J Raffel - Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
Karen D Hinckley Stukovsky - Department of Biostatistics, University of Washington, Seattle, Washington
James D Crapo - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado
Terri H Beaty - Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
John E Hokanson - Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado
Edwin K Silverman - Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, and
Josée Dupuis - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
George T O’Connor - The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; and
H. Marike Boezen - Department of Epidemiology
Stephen S Rich - Center for Public Health Genomics, and
R. Graham Barr - Department of Medicine, College of Physicians and Surgeons
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.189(4), pp.408-418
DOI: 10.1164/rccm.201306-1061OC
PMID: 24383474
PMCID: PMC3977717
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: American Thoracic Society
Language: English
Date published: 02/15/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051867702771

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