American journal of respiratory and critical care medicine · 2023

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

СтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Peljto Anna L, Blumhagen Rachel Z, Walts Avram D, Cardwell Jonathan, Powers Julia, Corte Tamera J, Dickinson Joanne L, Glaspole Ian, Moodley Yuben P, Vasakova Martina Koziar, Bendstrup Elisabeth, Davidsen Jesper R, Borie Raphael, Crestani Bruno, Dieude Philippe, Bonella Francesco, Costabel Ulrich, Gudmundsson Gunnar, Donnelly Seamas C, Egan Jim, Henry Michael T, Keane Michael P, Kennedy Marcus P, McCarthy Cormac, McElroy Aoife N, Olaniyi Joshua A, O'Reilly Katherine M A, Richeldi Luca, Leone Paolo M, Poletti Venerino, Puppo Francesco, Tomassetti Sara, Luzzi Valentina, Kokturk Nurdan, Mogulkoc Nesrin, Fiddler Christine A, Hirani Nikhil, Jenkins R Gisli, Maher Toby M, Molyneaux Philip L, Parfrey Helen, Braybrooke Rebecca, Blackwell Timothy S, Jackson Peter D, Nathan Steven D, Porteous Mary K, Brown Kevin K, Christie Jason D, Collard Harold R, Eickelberg Oliver, Foster Elena E, Gibson Kevin F, Glassberg Marilyn, Kass Daniel J, Kropski Jonathan A, Lederer David, Linderholm Angela L, Loyd Jim, Mathai Susan K, Montesi Sydney B, Noth Imre, Oldham Justin M, Palmisciano Amy J, Reichner Cristina A, Rojas Mauricio, Roman Jesse, Schluger Neil, Shea Barry S, Swigris Jeffrey J, Wolters Paul J, Zhang Yingze, Prele Cecilia M A, Enghelmayer Juan I, Otaola Maria, Ryerson Christopher J, Salinas Mauricio, Sterclova Martina, Gebremariam Tewodros H, Myllärniemi Marjukka, Carbone Roberto G, Furusawa Haruhiko, Hirose Masaki, Inoue Yoshikazu, Miyazaki Yasunari, Ohta Ken, Ohta Shin, Okamoto Tsukasa, Kim Dong Soon, Pardo Annie, Selman Moises, Aranda Alvaro U, Park Moo Suk, Park Jong Sun, Song Jin Woo, Molina-Molina Maria, Planas-Cerezales Lurdes, Westergren-Thorsson Gunilla, Smith Albert V, Manichaikul Ani W, Kim John S, Rich Stephen S, Oelsner Elizabeth C, Barr R Graham, Rotter Jerome I, Dupuis Josee, O'Connor George, Vasan Ramachandran S, Cho Michael H, Silverman Edwin K, Schwarz Marvin I, Steele Mark P, Lee Joyce S, Yang Ivana V, Fingerlin Tasha E, Schwartz David A

Аннотация

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Предметные рубрики MeSH

Humans Idiopathic Pulmonary Fibrosis Whole Genome Sequencing Exome

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH