Dataset Information

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.

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.

SUBMITTER: Manichaikul A

PROVIDER: S-EPMC3977717 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

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.

Manichaikul Ani A Hoffman Eric A EA Smolonska Joanna J Gao Wei W Cho Michael H MH Baumhauer Heather H Budoff Matthew M Austin John H M JH Washko George R GR Carr J Jeffrey JJ Kaufman Joel D JD Pottinger Tess T Powell Charles A CA Wijmenga Cisca C Zanen Pieter P Groen Harry J M HJ Postma Dirkje S DS Wanner Adam A Rouhani Farshid N FN Brantly Mark L ML Powell Rhea R Smith Benjamin M BM Rabinowitz Dan D Raffel Leslie J LJ Hinckley Stukovsky Karen D KD Crapo James D JD Beaty Terri H TH Hokanson John E JE Silverman Edwin K EK Dupuis Josée J O'Connor George T GT Boezen H Marike HM Rich Stephen S SS Barr R Graham RG

American journal of respiratory and critical care medicine 20140201 4

<h4>Rationale</h4>Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.<h4>Objectives</h4>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.<h4>Methods</h4>We deter ...[more]

PMID: 24383474

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Project description:BackgroundPulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics.MethodsThe Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ≥ 10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines.ResultsTwenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P <.001). Panlobular, but not other types of emphysema, was associated with reduced body mass index (-5 kg/m(2); P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance.ConclusionsEmphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences.

Dataset Information

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.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

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.

Similar Datasets

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