Genome-wide association study of subclinical interstitial lung disease in MESA
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 (HA...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-017-0581-2 |
| _version_ | 1818975825928650752 |
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| author | Ani Manichaikul Xin-Qun Wang Li Sun Josée Dupuis Alain C. Borczuk Jennifer N. Nguyen Ganesh Raghu Eric A. Hoffman Suna Onengut-Gumuscu Emily A. Farber Joel D. Kaufman Dan Rabinowitz Karen D. Hinckley Stukovsky Steven M. Kawut Gary M. Hunninghake George R. Washko George T. O’Connor Stephen S. Rich R. Graham Barr David J. Lederer |
| author_facet | Ani Manichaikul Xin-Qun Wang Li Sun Josée Dupuis Alain C. Borczuk Jennifer N. Nguyen Ganesh Raghu Eric A. Hoffman Suna Onengut-Gumuscu Emily A. Farber Joel D. Kaufman Dan Rabinowitz Karen D. Hinckley Stukovsky Steven M. Kawut Gary M. Hunninghake George R. Washko George T. O’Connor Stephen S. Rich R. Graham Barr David J. Lederer |
| author_sort | Ani Manichaikul |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T16:02:07Z |
| format | Article |
| id | doaj.art-8569ea883b4e41909cc97d17bf6d172b |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-20T16:02:07Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj.art-8569ea883b4e41909cc97d17bf6d172b2022-12-21T19:34:14ZengBMCRespiratory Research1465-993X2017-05-0118111110.1186/s12931-017-0581-2Genome-wide association study of subclinical interstitial lung disease in MESAAni Manichaikul0Xin-Qun Wang1Li Sun2Josée Dupuis3Alain C. Borczuk4Jennifer N. Nguyen5Ganesh Raghu6Eric A. Hoffman7Suna Onengut-Gumuscu8Emily A. Farber9Joel D. Kaufman10Dan Rabinowitz11Karen D. Hinckley Stukovsky12Steven M. Kawut13Gary M. Hunninghake14George R. Washko15George T. O’Connor16Stephen S. Rich17R. Graham Barr18David J. Lederer19Center for Public Health Genomics, University of VirginiaDepartment of Public Health Sciences, Biostatistics Section, University of VirginiaDepartment of Medicine, College of Physicians and Surgeons, Columbia UniversityDepartment of Biostatistics, Boston University School of Public HealthDepartment of Pathology, Weill Cornell MedicineCenter for Public Health Genomics, University of VirginiaUniversity of Washington Center for Interstitial Lung DiseasesDepartment of Radiology, University of Iowa Carver College of MedicineCenter for Public Health Genomics, University of VirginiaCenter for Public Health Genomics, University of VirginiaDepartmenst of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, University of WashingtonDepartment of Statistics, Columbia UniversityDepartment of Biostatistics, University of WashingtonDepartment of Medicine and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of PennsylvaniaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s HospitalDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s HospitalThe National Heart, Lung, and Blood Institute’s Framingham Heart StudyCenter for Public Health Genomics, University of VirginiaDepartment of Medicine, College of Physicians and Surgeons, Columbia UniversityDepartment of Medicine, College of Physicians and Surgeons, Columbia UniversityAbstract 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.http://link.springer.com/article/10.1186/s12931-017-0581-2Interstitial lung diseaseGeneticsGenome-wide association studyEpidemiology |
| spellingShingle | Ani Manichaikul Xin-Qun Wang Li Sun Josée Dupuis Alain C. Borczuk Jennifer N. Nguyen Ganesh Raghu Eric A. Hoffman Suna Onengut-Gumuscu Emily A. Farber Joel D. Kaufman Dan Rabinowitz Karen D. Hinckley Stukovsky Steven M. Kawut Gary M. Hunninghake George R. Washko George T. O’Connor Stephen S. Rich R. Graham Barr David J. Lederer Genome-wide association study of subclinical interstitial lung disease in MESA Respiratory Research Interstitial lung disease Genetics Genome-wide association study Epidemiology |
| title | Genome-wide association study of subclinical interstitial lung disease in MESA |
| title_full | Genome-wide association study of subclinical interstitial lung disease in MESA |
| title_fullStr | Genome-wide association study of subclinical interstitial lung disease in MESA |
| title_full_unstemmed | Genome-wide association study of subclinical interstitial lung disease in MESA |
| title_short | Genome-wide association study of subclinical interstitial lung disease in MESA |
| title_sort | genome wide association study of subclinical interstitial lung disease in mesa |
| topic | Interstitial lung disease Genetics Genome-wide association study Epidemiology |
| url | http://link.springer.com/article/10.1186/s12931-017-0581-2 |
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