Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis
Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known. To perform a genome-wide association...
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| creator | Hobbs, Brian D Putman, Rachel K Araki, Tetsuro Nishino, Mizuki Gudmundsson, Gunnar Gudnason, Vilmundur Eiriksdottir, Gudny Zilhao Nogueira, Nuno Rodrigues Dupuis, Josée Xu, Hanfei O'Connor, George T Manichaikul, Ani Nguyen, Jennifer Podolanczuk, Anna J Madahar, Purnema Rotter, Jerome I Lederer, David J Barr, R Graham Rich, Stephen S Ampleford, Elizabeth J Ortega, Victor E Peters, Stephen P O'Neal, Wanda K Newell, Jr, John D Bleecker, Eugene R Meyers, Deborah A Allen, Richard J Oldham, Justin M Ma, Shwu-Fan Noth, Imre Jenkins, R Gisli Maher, Toby M Hubbard, Richard B Wain, Louise V Fingerlin, Tasha E Schwartz, David A Washko, George R Rosas, Ivan O Silverman, Edwin K Hatabu, Hiroto Cho, Michael H Hunninghake, Gary M |
| description | Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.
To perform a genome-wide association study (GWAS) of ILAs.
ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.
Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The
(mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (
= 2.6 × 10
) and subpleural ILAs (
= 1.6 × 10
). We discovered novel genome-wide associations near
(rs6886640,
= 3.8 × 10
) and
(rs73199442,
= 4.8 × 10
) with ILAs, and near
(rs7744971,
= 4.2 × 10
) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (
,
,
,
, and
) were significantly associated (
|
| doi_str_mv | 10.1164/rccm.201903-0511OC |
| format | Article |
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To perform a genome-wide association study (GWAS) of ILAs.
ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.
Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The
(mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (
= 2.6 × 10
) and subpleural ILAs (
= 1.6 × 10
). We discovered novel genome-wide associations near
(rs6886640,
= 3.8 × 10
) and
(rs73199442,
= 4.8 × 10
) with ILAs, and near
(rs7744971,
= 4.2 × 10
) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (
,
,
,
, and
) were significantly associated (
< 0.05/12) with ILAs.
In a GWAS of ILAs in six studies, we confirmed the association with a
promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.</description><identifier>ISSN: 1073-449X</identifier><identifier>ISSN: 1535-4970</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.201903-0511OC</identifier><identifier>PMID: 31339356</identifier><language>eng</language><publisher>United States: American Thoracic Society</publisher><subject>Aged ; beta Karyopherins - genetics ; Biological products ; Case-Control Studies ; Female ; Genetic Loci ; Genetic Predisposition to Disease - genetics ; Genetics ; Genome-Wide Association Study ; Humans ; Idiopathic Pulmonary Fibrosis - genetics ; Lung diseases ; Lung Diseases, Interstitial - genetics ; Male ; Middle Aged ; Mucin-5B - genetics ; Original ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic - genetics ; Pulmonary fibrosis ; TATA Box Binding Protein-Like Proteins</subject><ispartof>American journal of respiratory and critical care medicine, 2019-12, Vol.200 (11), p.1402-1413</ispartof><rights>Copyright American Thoracic Society Dec 1, 2019</rights><rights>Copyright © 2019 by the American Thoracic Society 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-9564-0745 ; 0000-0002-9559-1485 ; 0000-0001-5258-0228 ; 0000-0002-8027-7450</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31339356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hobbs, Brian D</creatorcontrib><creatorcontrib>Putman, Rachel K</creatorcontrib><creatorcontrib>Araki, Tetsuro</creatorcontrib><creatorcontrib>Nishino, Mizuki</creatorcontrib><creatorcontrib>Gudmundsson, Gunnar</creatorcontrib><creatorcontrib>Gudnason, Vilmundur</creatorcontrib><creatorcontrib>Eiriksdottir, Gudny</creatorcontrib><creatorcontrib>Zilhao Nogueira, Nuno Rodrigues</creatorcontrib><creatorcontrib>Dupuis, Josée</creatorcontrib><creatorcontrib>Xu, Hanfei</creatorcontrib><creatorcontrib>O'Connor, George T</creatorcontrib><creatorcontrib>Manichaikul, Ani</creatorcontrib><creatorcontrib>Nguyen, Jennifer</creatorcontrib><creatorcontrib>Podolanczuk, Anna J</creatorcontrib><creatorcontrib>Madahar, Purnema</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Lederer, David J</creatorcontrib><creatorcontrib>Barr, R Graham</creatorcontrib><creatorcontrib>Rich, Stephen S</creatorcontrib><creatorcontrib>Ampleford, Elizabeth J</creatorcontrib><creatorcontrib>Ortega, Victor E</creatorcontrib><creatorcontrib>Peters, Stephen P</creatorcontrib><creatorcontrib>O'Neal, Wanda K</creatorcontrib><creatorcontrib>Newell, Jr, John D</creatorcontrib><creatorcontrib>Bleecker, Eugene R</creatorcontrib><creatorcontrib>Meyers, Deborah A</creatorcontrib><creatorcontrib>Allen, Richard J</creatorcontrib><creatorcontrib>Oldham, Justin M</creatorcontrib><creatorcontrib>Ma, Shwu-Fan</creatorcontrib><creatorcontrib>Noth, Imre</creatorcontrib><creatorcontrib>Jenkins, R Gisli</creatorcontrib><creatorcontrib>Maher, Toby M</creatorcontrib><creatorcontrib>Hubbard, Richard B</creatorcontrib><creatorcontrib>Wain, Louise V</creatorcontrib><creatorcontrib>Fingerlin, Tasha E</creatorcontrib><creatorcontrib>Schwartz, David A</creatorcontrib><creatorcontrib>Washko, George R</creatorcontrib><creatorcontrib>Rosas, Ivan O</creatorcontrib><creatorcontrib>Silverman, Edwin K</creatorcontrib><creatorcontrib>Hatabu, Hiroto</creatorcontrib><creatorcontrib>Cho, Michael H</creatorcontrib><creatorcontrib>Hunninghake, Gary M</creatorcontrib><title>Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.
To perform a genome-wide association study (GWAS) of ILAs.
ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.
Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The
(mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (
= 2.6 × 10
) and subpleural ILAs (
= 1.6 × 10
). We discovered novel genome-wide associations near
(rs6886640,
= 3.8 × 10
) and
(rs73199442,
= 4.8 × 10
) with ILAs, and near
(rs7744971,
= 4.2 × 10
) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (
,
,
,
, and
) were significantly associated (
< 0.05/12) with ILAs.
In a GWAS of ILAs in six studies, we confirmed the association with a
promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.</description><subject>Aged</subject><subject>beta Karyopherins - genetics</subject><subject>Biological products</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Idiopathic Pulmonary Fibrosis - genetics</subject><subject>Lung diseases</subject><subject>Lung Diseases, Interstitial - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mucin-5B - genetics</subject><subject>Original</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Pulmonary fibrosis</subject><subject>TATA Box Binding Protein-Like Proteins</subject><issn>1073-449X</issn><issn>1535-4970</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkNFqFTEQhoMotlZfwAsJeOPN1kwm2WxuhHKw9cCBI6WCd0s2m9Om7iZrkq307RuxigoDM8z88_HPEPIa2ClAK94na-dTzkAzbJgE2G-ekGOQKBuhFXtaa6awEUJ_PSIvcr5lDHgH7Dk5QkDUKNtjYvZ3Lk1mofFAL1xwxVt66fM3Orjyw7lAt6G4lIsv3kx0t4ZrejaEmGYz1ZbL1ISRbkcfF1Nu6u7ndZpjMOmenvshxezzS_LsYKbsXj3mE_Ll_OPV5lOz219sN2e7ZuFclKbDUbX6gB0bOzgMg61ngVQcQXUgtcRWWFRixNbKsdPMCqZbra0DHJxUHZ6QD7-4yzrMbrQulGSmfkl-rnb6aHz_7yT4m_463vVt1wkmZAW8ewSk-H11ufSzz9ZNkwkurrnnvEXkIJSq0rf_SW_jmkI9r-coawCwn8A3fzv6Y-X39_EB2XyIHQ</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Hobbs, Brian D</creator><creator>Putman, Rachel K</creator><creator>Araki, Tetsuro</creator><creator>Nishino, Mizuki</creator><creator>Gudmundsson, Gunnar</creator><creator>Gudnason, Vilmundur</creator><creator>Eiriksdottir, Gudny</creator><creator>Zilhao Nogueira, Nuno Rodrigues</creator><creator>Dupuis, Josée</creator><creator>Xu, Hanfei</creator><creator>O'Connor, George T</creator><creator>Manichaikul, Ani</creator><creator>Nguyen, Jennifer</creator><creator>Podolanczuk, Anna J</creator><creator>Madahar, Purnema</creator><creator>Rotter, Jerome I</creator><creator>Lederer, David J</creator><creator>Barr, R Graham</creator><creator>Rich, Stephen S</creator><creator>Ampleford, Elizabeth J</creator><creator>Ortega, Victor E</creator><creator>Peters, Stephen P</creator><creator>O'Neal, Wanda K</creator><creator>Newell, Jr, John D</creator><creator>Bleecker, Eugene R</creator><creator>Meyers, Deborah A</creator><creator>Allen, Richard J</creator><creator>Oldham, Justin M</creator><creator>Ma, Shwu-Fan</creator><creator>Noth, Imre</creator><creator>Jenkins, R Gisli</creator><creator>Maher, Toby M</creator><creator>Hubbard, Richard B</creator><creator>Wain, Louise V</creator><creator>Fingerlin, Tasha E</creator><creator>Schwartz, David A</creator><creator>Washko, George R</creator><creator>Rosas, Ivan O</creator><creator>Silverman, Edwin K</creator><creator>Hatabu, Hiroto</creator><creator>Cho, Michael H</creator><creator>Hunninghake, Gary M</creator><general>American Thoracic Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9564-0745</orcidid><orcidid>https://orcid.org/0000-0002-9559-1485</orcidid><orcidid>https://orcid.org/0000-0001-5258-0228</orcidid><orcidid>https://orcid.org/0000-0002-8027-7450</orcidid></search><sort><creationdate>20191201</creationdate><title>Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis</title><author>Hobbs, Brian D ; Putman, Rachel K ; Araki, Tetsuro ; Nishino, Mizuki ; Gudmundsson, Gunnar ; Gudnason, Vilmundur ; Eiriksdottir, Gudny ; Zilhao Nogueira, Nuno Rodrigues ; Dupuis, Josée ; Xu, Hanfei ; O'Connor, George T ; Manichaikul, Ani ; Nguyen, Jennifer ; Podolanczuk, Anna J ; Madahar, Purnema ; Rotter, Jerome I ; Lederer, David J ; Barr, R Graham ; Rich, Stephen S ; Ampleford, Elizabeth J ; Ortega, Victor E ; Peters, Stephen P ; O'Neal, Wanda K ; Newell, Jr, John D ; Bleecker, Eugene R ; Meyers, Deborah A ; Allen, Richard J ; Oldham, Justin M ; Ma, Shwu-Fan ; Noth, Imre ; Jenkins, R Gisli ; Maher, Toby M ; Hubbard, Richard B ; Wain, Louise V ; Fingerlin, Tasha E ; Schwartz, David A ; Washko, George R ; Rosas, Ivan O ; Silverman, Edwin K ; Hatabu, Hiroto ; Cho, Michael H ; Hunninghake, Gary M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p224t-83d769f380d81fbbc190157231781595364c374d36c5d890c409699ce13be5783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>beta Karyopherins - genetics</topic><topic>Biological products</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Loci</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetics</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Idiopathic Pulmonary Fibrosis - genetics</topic><topic>Lung diseases</topic><topic>Lung Diseases, Interstitial - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mucin-5B - genetics</topic><topic>Original</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Pulmonary fibrosis</topic><topic>TATA Box Binding Protein-Like Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hobbs, Brian D</creatorcontrib><creatorcontrib>Putman, Rachel K</creatorcontrib><creatorcontrib>Araki, Tetsuro</creatorcontrib><creatorcontrib>Nishino, Mizuki</creatorcontrib><creatorcontrib>Gudmundsson, Gunnar</creatorcontrib><creatorcontrib>Gudnason, Vilmundur</creatorcontrib><creatorcontrib>Eiriksdottir, Gudny</creatorcontrib><creatorcontrib>Zilhao Nogueira, Nuno Rodrigues</creatorcontrib><creatorcontrib>Dupuis, Josée</creatorcontrib><creatorcontrib>Xu, Hanfei</creatorcontrib><creatorcontrib>O'Connor, George T</creatorcontrib><creatorcontrib>Manichaikul, Ani</creatorcontrib><creatorcontrib>Nguyen, Jennifer</creatorcontrib><creatorcontrib>Podolanczuk, Anna J</creatorcontrib><creatorcontrib>Madahar, Purnema</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Lederer, David J</creatorcontrib><creatorcontrib>Barr, R Graham</creatorcontrib><creatorcontrib>Rich, Stephen S</creatorcontrib><creatorcontrib>Ampleford, Elizabeth J</creatorcontrib><creatorcontrib>Ortega, Victor E</creatorcontrib><creatorcontrib>Peters, Stephen P</creatorcontrib><creatorcontrib>O'Neal, Wanda K</creatorcontrib><creatorcontrib>Newell, Jr, John D</creatorcontrib><creatorcontrib>Bleecker, Eugene R</creatorcontrib><creatorcontrib>Meyers, Deborah A</creatorcontrib><creatorcontrib>Allen, Richard J</creatorcontrib><creatorcontrib>Oldham, Justin M</creatorcontrib><creatorcontrib>Ma, Shwu-Fan</creatorcontrib><creatorcontrib>Noth, Imre</creatorcontrib><creatorcontrib>Jenkins, R Gisli</creatorcontrib><creatorcontrib>Maher, Toby M</creatorcontrib><creatorcontrib>Hubbard, Richard B</creatorcontrib><creatorcontrib>Wain, Louise V</creatorcontrib><creatorcontrib>Fingerlin, Tasha E</creatorcontrib><creatorcontrib>Schwartz, David A</creatorcontrib><creatorcontrib>Washko, George R</creatorcontrib><creatorcontrib>Rosas, Ivan O</creatorcontrib><creatorcontrib>Silverman, Edwin K</creatorcontrib><creatorcontrib>Hatabu, Hiroto</creatorcontrib><creatorcontrib>Cho, Michael H</creatorcontrib><creatorcontrib>Hunninghake, Gary M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hobbs, Brian D</au><au>Putman, Rachel K</au><au>Araki, Tetsuro</au><au>Nishino, Mizuki</au><au>Gudmundsson, Gunnar</au><au>Gudnason, Vilmundur</au><au>Eiriksdottir, Gudny</au><au>Zilhao Nogueira, Nuno Rodrigues</au><au>Dupuis, Josée</au><au>Xu, Hanfei</au><au>O'Connor, George T</au><au>Manichaikul, Ani</au><au>Nguyen, Jennifer</au><au>Podolanczuk, Anna J</au><au>Madahar, Purnema</au><au>Rotter, Jerome I</au><au>Lederer, David J</au><au>Barr, R Graham</au><au>Rich, Stephen S</au><au>Ampleford, Elizabeth J</au><au>Ortega, Victor E</au><au>Peters, Stephen P</au><au>O'Neal, Wanda K</au><au>Newell, Jr, John D</au><au>Bleecker, Eugene R</au><au>Meyers, Deborah A</au><au>Allen, Richard J</au><au>Oldham, Justin M</au><au>Ma, Shwu-Fan</au><au>Noth, Imre</au><au>Jenkins, R Gisli</au><au>Maher, Toby M</au><au>Hubbard, Richard B</au><au>Wain, Louise V</au><au>Fingerlin, Tasha E</au><au>Schwartz, David A</au><au>Washko, George R</au><au>Rosas, Ivan O</au><au>Silverman, Edwin K</au><au>Hatabu, Hiroto</au><au>Cho, Michael H</au><au>Hunninghake, Gary M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>200</volume><issue>11</issue><spage>1402</spage><epage>1413</epage><pages>1402-1413</pages><issn>1073-449X</issn><issn>1535-4970</issn><eissn>1535-4970</eissn><abstract>Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.
To perform a genome-wide association study (GWAS) of ILAs.
ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.
Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The
(mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (
= 2.6 × 10
) and subpleural ILAs (
= 1.6 × 10
). We discovered novel genome-wide associations near
(rs6886640,
= 3.8 × 10
) and
(rs73199442,
= 4.8 × 10
) with ILAs, and near
(rs7744971,
= 4.2 × 10
) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (
,
,
,
, and
) were significantly associated (
< 0.05/12) with ILAs.
In a GWAS of ILAs in six studies, we confirmed the association with a
promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.</abstract><cop>United States</cop><pub>American Thoracic Society</pub><pmid>31339356</pmid><doi>10.1164/rccm.201903-0511OC</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9564-0745</orcidid><orcidid>https://orcid.org/0000-0002-9559-1485</orcidid><orcidid>https://orcid.org/0000-0001-5258-0228</orcidid><orcidid>https://orcid.org/0000-0002-8027-7450</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1073-449X |
| ispartof | American journal of respiratory and critical care medicine, 2019-12, Vol.200 (11), p.1402-1413 |
| issn | 1073-449X 1535-4970 1535-4970 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6884045 |
| source | MEDLINE; American Thoracic Society Journals; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Aged beta Karyopherins - genetics Biological products Case-Control Studies Female Genetic Loci Genetic Predisposition to Disease - genetics Genetics Genome-Wide Association Study Humans Idiopathic Pulmonary Fibrosis - genetics Lung diseases Lung Diseases, Interstitial - genetics Male Middle Aged Mucin-5B - genetics Original Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic - genetics Pulmonary fibrosis TATA Box Binding Protein-Like Proteins |
| title | Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T19%3A35%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Overlap%20of%20Genetic%20Risk%20between%20Interstitial%20Lung%20Abnormalities%20and%20Idiopathic%20Pulmonary%20Fibrosis&rft.jtitle=American%20journal%20of%20respiratory%20and%20critical%20care%20medicine&rft.au=Hobbs,%20Brian%20D&rft.date=2019-12-01&rft.volume=200&rft.issue=11&rft.spage=1402&rft.epage=1413&rft.pages=1402-1413&rft.issn=1073-449X&rft.eissn=1535-4970&rft_id=info:doi/10.1164/rccm.201903-0511OC&rft_dat=%3Cproquest_pubme%3E2352351105%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2352351105&rft_id=info:pmid/31339356&rfr_iscdi=true |