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Genome-wide association study of subclinical interstitial lung disease in MESA
- Source :
- Respiratory Research, Vol 18, Iss 1, Pp 1-11 (2017), Respiratory Research
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Background We conducted a genome-wide association study (GWAS) of subclinical interstitial lung disease (ILD), defined as high attenuation areas (HAA) on CT, in the population-based Multi-Ethnic Study of Atherosclerosis Study. Methods We measured the percentage of high attenuation areas (HAA) in the lung fields on cardiac CT scan defined as voxels with CT attenuation values between -600 and -250 HU. Genetic analyses were performed in MESA combined across race/ethnic groups: non-Hispanic White (n = 2,434), African American (n = 2,470), Hispanic (n = 2,065) and Chinese (n = 702), as well as stratified by race/ethnicity. Results Among 7,671 participants, regions at genome-wide significance were identified for basilar peel-core ratio of HAA in FLJ35282 downstream of ANRIL (rs7852363, P = 2.1x10−9) and within introns of SNAI3-AS1 (rs140142658, P = 9.6x10−9) and D21S2088E (rs3079677, P = 2.3x10−8). Within race/ethnic groups, 18 additional loci were identified at genome-wide significance, including genes related to development (FOXP4), cell adhesion (ALCAM) and glycosylation (GNPDA2, GYPC, GFPT1 and FUT10). Among these loci, SNP rs6844387 near GNPDA2 demonstrated nominal evidence of replication in analysis of n = 1,959 participants from the Framingham Heart Study (P = 0.029). FOXP4 region SNP rs2894439 demonstrated evidence of validation in analysis of n = 228 White ILD cases from the Columbia ILD Study compared to race/ethnicity-matched controls from MESA (one-sided P = 0.007). In lung tissue from 15 adults with idiopathic pulmonary fibrosis compared to 15 adults without lung disease. ANRIL (P = 0.001), ALCAM (P = 0.03) and FOXP4 (P = 0.046) were differentially expressed. Conclusions Our results suggest novel roles for protein glycosylation and cell cycle disinhibition by long non-coding RNA in the pathogenesis of ILD. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0581-2) contains supplementary material, which is available to authorized users.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Genome-wide association study
medicine.medical_specialty
Pathology
Epidemiology
Population
Interstitial lung disease
Polymorphism, Single Nucleotide
White People
03 medical and health sciences
Idiopathic pulmonary fibrosis
0302 clinical medicine
Framingham Heart Study
Asian People
Internal medicine
Genetics
medicine
Humans
SNP
Longitudinal Studies
education
Aged
Subclinical infection
Aged, 80 and over
lcsh:RC705-779
education.field_of_study
Lung
business.industry
Research
Hispanic or Latino
lcsh:Diseases of the respiratory system
Middle Aged
medicine.disease
3. Good health
Black or African American
030104 developmental biology
medicine.anatomical_structure
Population Surveillance
030220 oncology & carcinogenesis
Female
Lung Diseases, Interstitial
business
Subjects
Details
- ISSN :
- 1465993X
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....04a2522e3972b5b086e741519b6aae2d