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IRIS PubliCatt
Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic 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 variants that are influential within genes and estimated the heritability of IPF based on 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% (s.e. 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 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.
Peljto, A. L., Blumhagen, R. Z., Walts, A. D., Cardwell, J., Powers, J., Corte, T. J., Dickinson, J. L., Glaspole, I., Moodley, Y. P., Vasakova, M. K., Bendstrup, E., Davidsen, J. R., Borie, R., Crestani, B., Dieude, P., Bonella, F., Costabel, U., Gudmundsson, G., Donnelly, S. C., Egan, J., Henry, M. T., Keane, M. P., Kennedy, M. P., Mccarthy, C., Mcelroy, A. N., Olaniyi, J. A., O'Reilly, K. M. A., Richeldi, L., Leone, P. M., Poletti, V., Puppo, F., Tomassetti, S., Luzzi, V., Kokturk, N., Mogulkoc, N., Fiddler, C. A., Hirani, N., Jenkins, G., Maher, T. M., Molyneaux, P. L., Parfrey, H., Braybrooke, R., Blackwell, T. S., Jackson, P. D., Nathan, S. D., Porteous, M. K., Brown, K. K., Christie, J. D., Collard, H. R., Eickelberg, O., Foster, E. E., Gibson, K. F., Glassberg, M., Kass, D., Kropski, J. A., Lederer, D., Linderholm, A. L., Loyd, J., Mathai, S. K., Montesi, S. B., Noth, I., Oldham, J. M., Palmisciano, A. J., Reichner, C. A., Rojas, M., Roman, J., Schluger, N., Shea, B. S., Swigris, J. J., Wolters, P. J., Zhang, Y., Prele, C. M. A., Enghelmayer, J. I., Otaola, M., Ryerson, C. J., Salinas, M., Sterclova, M., Gebremariam, T. H., Myllärniemi, M., Carbone, R., Furusawa, H., Hirose, M., Inoue, Y., Miyazaki, Y., Ohta, K., Ohta, S., Okamoto, T., Kim, D. S., Pardo, A., Selman, M., Aranda, A. U., Park, M. S., Park, J. S., Song, J. W., Molina-Molina, M., Planas-Cerezales, L., Westergren-Thorsson, G., Smith, A. V., Manichaikul, A. W., Kim, J. S., Rich, S. S., Oelsner, E. C., Barr, R. G., Rotter, J. I., Dupuis, J., O'Connor, G., Vasan, R. S., Cho, M. H., Silverman, E. K., Schwarz, M. I., Steele, M. P., Lee, J. S., Yang, I. V., Fingerlin, T. E., Schwartz, D. A., Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants, <<AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE>>, 2023; 2023 (Jan 5): 1-5. [doi:10.1164/rccm.202207-1331OC] [https://hdl.handle.net/10807/233027]
Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants
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 Maria;Poletti, Venerino;Puppo, Francesco;Tomassetti, Sara;Luzzi, Valentina;Kokturk, Nurdan;Mogulkoc, Nesrin;Fiddler, Christine A;Hirani, Nikhil;Jenkins, 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;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;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
2023
Abstract
Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic 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 variants that are influential within genes and estimated the heritability of IPF based on 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% (s.e. 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 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.
Peljto, A. L., Blumhagen, R. Z., Walts, A. D., Cardwell, J., Powers, J., Corte, T. J., Dickinson, J. L., Glaspole, I., Moodley, Y. P., Vasakova, M. K., Bendstrup, E., Davidsen, J. R., Borie, R., Crestani, B., Dieude, P., Bonella, F., Costabel, U., Gudmundsson, G., Donnelly, S. C., Egan, J., Henry, M. T., Keane, M. P., Kennedy, M. P., Mccarthy, C., Mcelroy, A. N., Olaniyi, J. A., O'Reilly, K. M. A., Richeldi, L., Leone, P. M., Poletti, V., Puppo, F., Tomassetti, S., Luzzi, V., Kokturk, N., Mogulkoc, N., Fiddler, C. A., Hirani, N., Jenkins, G., Maher, T. M., Molyneaux, P. L., Parfrey, H., Braybrooke, R., Blackwell, T. S., Jackson, P. D., Nathan, S. D., Porteous, M. K., Brown, K. K., Christie, J. D., Collard, H. R., Eickelberg, O., Foster, E. E., Gibson, K. F., Glassberg, M., Kass, D., Kropski, J. A., Lederer, D., Linderholm, A. L., Loyd, J., Mathai, S. K., Montesi, S. B., Noth, I., Oldham, J. M., Palmisciano, A. J., Reichner, C. A., Rojas, M., Roman, J., Schluger, N., Shea, B. S., Swigris, J. J., Wolters, P. J., Zhang, Y., Prele, C. M. A., Enghelmayer, J. I., Otaola, M., Ryerson, C. J., Salinas, M., Sterclova, M., Gebremariam, T. H., Myllärniemi, M., Carbone, R., Furusawa, H., Hirose, M., Inoue, Y., Miyazaki, Y., Ohta, K., Ohta, S., Okamoto, T., Kim, D. S., Pardo, A., Selman, M., Aranda, A. U., Park, M. S., Park, J. S., Song, J. W., Molina-Molina, M., Planas-Cerezales, L., Westergren-Thorsson, G., Smith, A. V., Manichaikul, A. W., Kim, J. S., Rich, S. S., Oelsner, E. C., Barr, R. G., Rotter, J. I., Dupuis, J., O'Connor, G., Vasan, R. S., Cho, M. H., Silverman, E. K., Schwarz, M. I., Steele, M. P., Lee, J. S., Yang, I. V., Fingerlin, T. E., Schwartz, D. A., Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants, <<AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE>>, 2023; 2023 (Jan 5): 1-5. [doi:10.1164/rccm.202207-1331OC] [https://hdl.handle.net/10807/233027]
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2021-2023 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.