Journal article
Genome-wide association study of subclinical interstitial lung disease in MESA
Respiratory research, Vol.18(1), pp.97-97
05/18/2017
DOI: 10.1186/s12931-017-0581-2
PMCID: PMC5437638
PMID: 28521775
Abstract
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.
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.
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
) and within introns of SNAI3-AS1 (rs140142658, P = 9.6x10
) and D21S2088E (rs3079677, P = 2.3x10
). 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.
Our results suggest novel roles for protein glycosylation and cell cycle disinhibition by long non-coding RNA in the pathogenesis of ILD.
Details
- Title: Subtitle
- Genome-wide association study of subclinical interstitial lung disease in MESA
- Creators
- Ani Manichaikul - Center for Public Health Genomics, University of Virginia School of Medicine, West Complex Room 6115, Charlottesville, VA, 22903, USA. amanicha@virginia.eduXin-Qun Wang - Department of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, VA, USALi Sun - Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USAJosée Dupuis - The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USAAlain C Borczuk - Department of Pathology, Weill Cornell Medicine, New York, NY, USAJennifer N Nguyen - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USAGanesh Raghu - University of Washington Center for Interstitial Lung Diseases, Seattle, WA, USAEric A Hoffman - Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA, USASuna Onengut-Gumuscu - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USAEmily A Farber - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USAJoel D Kaufman - Departmenst of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, University of Washington, Seattle, WA, USADan Rabinowitz - Department of Statistics, Columbia University, New York, NY, USAKaren D Hinckley Stukovsky - Department of Biostatistics, University of Washington, Seattle, WA, USASteven M Kawut - Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAGary M Hunninghake - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USAGeorge R Washko - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USAGeorge T O'Connor - Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USAStephen S Rich - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USAR Graham Barr - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USADavid J Lederer - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.18(1), pp.97-97
- DOI
- 10.1186/s12931-017-0581-2
- PMID
- 28521775
- PMCID
- PMC5437638
- NLM abbreviation
- Respir Res
- ISSN
- 1465-9921
- eISSN
- 1465-993X
- Publisher
- England
- Grant note
- K23 HL086714 / NHLBI NIH HHS N01HC95169 / NHLBI NIH HHS N01HC95161 / NHLBI NIH HHS R01 HL071250 / NHLBI NIH HHS KL2 TR000081 / NCATS NIH HHS N01HC95164 / NHLBI NIH HHS R01 HL071051 / NHLBI NIH HHS N01HC95167 / NHLBI NIH HHS RC1 HL100543 / NHLBI NIH HHS R01 HL071251 / NHLBI NIH HHS N02HL64278 / NHLBI NIH HHS N01HC95159 / NHLBI NIH HHS R01 HL103676 / NHLBI NIH HHS N01HC95163 / NHLBI NIH HHS R01 HL077612 / NHLBI NIH HHS N01HC95166 / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS UL1 TR000124 / NCATS NIH HHS P30 ES005605 / NIEHS NIH HHS R01 HL131565 / NHLBI NIH HHS R01 HL093081 / NHLBI NIH HHS HHSN268201500003C / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS R01 HL112986 / NHLBI NIH HHS R01 HL071259 / NHLBI NIH HHS N01HC25195 / NHLBI NIH HHS UL1 RR033176 / NCRR NIH HHS R01 HL071205 / NHLBI NIH HHS R01 HL111024 / NHLBI NIH HHS UL1 TR000040 / NCATS NIH HHS R01 HL071258 / NHLBI NIH HHS N01HC95168 / NHLBI NIH HHS K24 HL131937 / NHLBI NIH HHS N01HC95165 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS P30 DK063491 / NIDDK NIH HHS N01HC95162 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/18/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984051513102771
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