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PubMed · 42085270

Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.

Anna L Peljto·Haruhiko Furusawa·Deepa Puthenvedu·Joyce S Lee·Mark P Steele·Janna Brancato·Jonathan Cardwell·Rachel Z Blumhagen·Joao de Andrade·Elisabeth Bendstrup·Timothy S Blackwell·Francesco Bonella·Raphael Borie·Rebecca Braybrooke·Kevin K Brown·Roberto G Carbone·Jason D Christie·Ulrich Costabel·Bruno Crestani·Jesper R Davidsen·Philippe Dieude·Seamas C Donnelly·Jim Egan·Oliver Eickelberg·Evans R Fernández Pérez·Christine A Fiddler·Elena E Foster·Kevin F Gibson·Gunnar Gudmundsson·Joel M Guthridge·Michael T Henry·Nikhil Hirani·R Gisli Jenkins·Daniel J Kass·Michael P Keane·Nurdan Kokturk·Jonathan A Kropski·David Lederer·Paolo M Leone·Angela L Linderholm·Toby M Maher·Susan K Mathai·Cormac McCarthy·Aoife N McElroy·Nesrin Mogulkoc·Maria Molina-Molina·Philip L Molyneaux·Sydney B Montesi·Steven D Nathan·Imre Noth·Joshua A Olaniyi·Justin M Oldham·Katherine M A O'Reilly·Amy J Palmisciano·Annie Pardo·Helen Parfrey·Lurdes Planas-Cerezales·Venerino Poletti·Mary K Porteous·Francesco Puppo·Luca Richeldi·Mauricio Rojas·Mauricio Salinas·Neil Schluger·Moises Selman·Barry S Shea·Martina Sterclova·Joshua J Solomon·Sara Tomassetti·Martina Koziar Vasakova·Yingze Zhang·Tamera J Corte·Joanne L Dickinson·Ian Glaspole·Yuben P Moodley·Cecilia M A Prele·Christopher J Ryerson·Paul J Wolters·Megumi Jinno·Yoshito Miyata·Shinobu Akagawa·Osamu Narumoto·Toshiyuki Kita·Takuo Shibayama·Toshihiko Li·Isoko Owan·Kentaro Wakamatsu·Toru Arai·Masaki Hirose·Dong Soon Kim·Ken Ohta·Shin Ohta·Jong Sun Park·Moo Suk Park·Ivana V Yang·Tasha E Fingerlin·Yasunari Miyazaki·Tsukasa Okamoto·Yoshikazu Inoue·Jin Woo Song
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Abstract

RATIONALE: Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES: To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS: We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS: We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS: We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

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AgedFemaleHumansMaleMiddle AgedEuropean PeopleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyIdiopathic Pulmonary FibrosisJapanPolymorphism, Single NucleotideRisk FactorsWhite PeopleEast Asian Peoplehuman geneticsinterstitial lung diseasepulmonary fibrosisJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Anna L Peljto, Haruhiko Furusawa, Deepa Puthenvedu, Joyce S Lee, Mark P Steele, Janna Brancato, Jonathan Cardwell, Rachel Z Blumhagen, Joao de Andrade, Elisabeth Bendstrup, Timothy S Blackwell, Francesco Bonella, Raphael Borie, Rebecca Braybrooke, Kevin K Brown, Roberto G Carbone, Jason D Christie, Ulrich Costabel, Bruno Crestani, Jesper R Davidsen, Philippe Dieude, Seamas C Donnelly, Jim Egan, Oliver Eickelberg, Evans R Fernández Pérez, Christine A Fiddler, Elena E Foster, Kevin F Gibson, Gunnar Gudmundsson, Joel M Guthridge, Michael T Henry, Nikhil Hirani, R Gisli Jenkins, Daniel J Kass, Michael P Keane, Nurdan Kokturk, Jonathan A Kropski, David Lederer, Paolo M Leone, Angela L Linderholm, Toby M Maher, Susan K Mathai, Cormac McCarthy, Aoife N McElroy, Nesrin Mogulkoc, Maria Molina-Molina, Philip L Molyneaux, Sydney B Montesi, Steven D Nathan, Imre Noth, Joshua A Olaniyi, Justin M Oldham, Katherine M A O'Reilly, Amy J Palmisciano, Annie Pardo, Helen Parfrey, Lurdes Planas-Cerezales, Venerino Poletti, Mary K Porteous, Francesco Puppo, Luca Richeldi, Mauricio Rojas, Mauricio Salinas, Neil Schluger, Moises Selman, Barry S Shea, Martina Sterclova, Joshua J Solomon, Sara Tomassetti, Martina Koziar Vasakova, Yingze Zhang, Tamera J Corte, Joanne L Dickinson, Ian Glaspole, Yuben P Moodley, Cecilia M A Prele, Christopher J Ryerson, Paul J Wolters, Megumi Jinno, Yoshito Miyata, Shinobu Akagawa, Osamu Narumoto, Toshiyuki Kita, Takuo Shibayama, Toshihiko Li, Isoko Owan, Kentaro Wakamatsu, Toru Arai, Masaki Hirose, Dong Soon Kim, Ken Ohta, Shin Ohta, Jong Sun Park, Moo Suk Park, Ivana V Yang, Tasha E Fingerlin, Yasunari Miyazaki, Tsukasa Okamoto, Yoshikazu Inoue, Jin Woo Song. 2026-07-01. Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.. https://doi.org/10.1093/ajrccm%2Faamag152

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