title: The genetic basis of idiopathic pulmonary fibrosis.
abstract: Throughout the past decade, there have been substantial advances in understanding the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recently, several large genome-wide association and linkage studies have identified common genetic variants in more than a dozen loci that appear to contribute to IPF risk. In addition, family-based studies have led to the identification of rare genetic variants in genes related to surfactant function and telomere biology, and mechanistic studies suggest pathophysiological derangements associated with these rare genetic variants are also found in sporadic cases of IPF. Current evidence suggests that rather than existing as distinct syndromes, sporadic and familial cases of IPF (familial interstitial pneumonia) probably reflect a continuum of genetic risk. Rapidly evolving bioinformatic and molecular biology techniques, combined with next-generation sequencing technologies, hold great promise for developing a comprehensive, integrated approach to defining the fundamental molecular mechanisms that underlie IPF pathogenesis.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Dept of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA jon.kropski@vanderbilt.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kropski
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Dept of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Dept of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA Dept of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA Department of Veterans Affairs Medical Center, Nashville, TN, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Dept of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
mesh_terms: D004265:DNA Helicases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D017563:Lung Diseases, Interstitial / Q000235:genetics; D055257:Mucin-5B / Q000235:genetics; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C524578:MUC5B protein, human; D055257:Mucin-5B; D037661:Pulmonary Surfactant-Associated Proteins; C410602:TOLLIP protein, human; C509186:TERT protein, human; D019098:Telomerase; C532890:RTEL1 protein, human; D004265:DNA Helicases
references.citation: Respir Res. 2014;15:43
references.pmid: 24730976
references.citation: Am J Respir Cell Mol Biol. 2011 Mar;44(3):404-14
references.pmid: 20463293
references.citation: Clin Exp Immunol. 2011 Dec;166(3):346-51
references.pmid: 22059992
references.citation: Dis Model Mech. 2013 Jan;6(1):9-17
references.pmid: 23268535
references.citation: Lung. 2013 Apr;191(2):199-205
references.pmid: 23344525
references.citation: J Biol Chem. 2010 Jul 16;285(29):22103-13
references.pmid: 20466729
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2013 Oct;30(3):221-5
references.pmid: 24284296
references.citation: J Cell Sci. 2003 Feb 15;116(Pt 4):683-92
references.pmid: 12538769
references.citation: Hum Mutat. 2013 Nov;34(11):1481-5
references.pmid: 23946118
references.citation: Chest. 2015 May;147(5):1361-8
references.pmid: 25539146
references.citation: J Biol Chem. 2013 Sep 20;288(38):27159-71
references.pmid: 23926107
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8222-7
references.pmid: 15928077
references.citation: Thorax. 2004 Nov;59(11):977-80
references.pmid: 15516475
references.citation: Dis Chest. 1950 Oct;18(4):330-44
references.pmid: 14778377
references.citation: Lancet Respir Med. 2014 May;2(5):416-28
references.pmid: 24815806
references.citation: J Med Genet. 2014 Aug;51(8):537-44
references.pmid: 24987033
references.citation: Eur Respir J. 2014 Feb;43(2):638-41
references.pmid: 24136335
references.citation: Nat Genet. 2013 Jun;45(6):613-20
references.pmid: 23583980
references.citation: Eur Respir J. 2014 Jul;44(1):178-87
references.pmid: 24833766
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1119-26
references.pmid: 18390830
references.citation: Chest. 2014 Jul;146(1):e1-7
references.pmid: 24504062
references.citation: Nat Biotechnol. 2013 Mar;31(3):230-2
references.pmid: 23360966
references.citation: N Engl J Med. 2011 Apr 21;364(16):1576-7
references.pmid: 21506748
references.citation: N Engl J Med. 2014 May 29;370(22):2083-92
references.pmid: 24836312
references.citation: PLoS One. 2013;8(3):e58658
references.pmid: 23527003
references.citation: N Engl J Med. 2001 Feb 22;344(8):573-9
references.pmid: 11207353
references.citation: Exp Lung Res. 2012 Apr;38(3):124-34
references.pmid: 22394286
references.citation: Nat Rev Cardiol. 2013 Sep;10(9):531-47
references.pmid: 23900355
references.citation: J Clin Invest. 2013 Nov;123(11):4950-62
references.pmid: 24135142
references.citation: Thorax. 2011 Oct;66(10):918-9
references.pmid: 21248320
references.citation: Lung. 2013 Oct;191(5):475-81
references.pmid: 23867963
references.citation: Mutat Res. 2012 Feb 1;730(1-2):52-8
references.pmid: 22079513
references.citation: Am J Hum Genet. 2006 Jul;79(1):149-54
references.pmid: 16773575
references.citation: Nature. 2014 Jan 16;505(7483):412-6
references.pmid: 24317696
references.citation: Respir Res. 2011;12:73
references.pmid: 21649933
references.citation: Chest. 2015 Feb;147(2):460-4
references.pmid: 25275363
references.citation: Eur Respir J. 2013 Dec;42(6):1757-9
references.pmid: 24072216
references.citation: Am J Respir Crit Care Med. 2003 Aug 15;168(4):431-5
references.pmid: 12746254
references.citation: Thorax. 2002 Apr;57(4):338-42
references.pmid: 11923553
references.citation: N Engl J Med. 2009 Dec 10;361(24):2353-65
references.pmid: 20007561
references.citation: Traffic. 2011 Sep;12(9):1196-210
references.pmid: 21707890
references.citation: Nat Biotechnol. 2014 Jul;32(7):663-9
references.pmid: 24837662
references.citation: Nat Neurosci. 2014 Jan;17(1):17-23
references.pmid: 24369373
references.citation: Chest. 2012 Dec;142(6):1584-8
references.pmid: 22576636
references.citation: Methods Enzymol. 2011;489:147-64
references.pmid: 21266229
references.citation: Immunogenetics. 2012 May;64(5):371-7
references.pmid: 22322675
references.citation: PLoS One. 2012;7(1):e30442
references.pmid: 22291954
references.citation: Clin Genet. 2015 Oct;88(4):344-51
references.pmid: 25263618
references.citation: J Clin Invest. 2007 Dec;117(12):3800-9
references.pmid: 18008008
references.citation: Respirology. 2015 Apr;20(3):439-44
references.pmid: 25581455
references.citation: Lancet Respir Med. 2013 Jun;1(4):309-17
references.pmid: 24429156
references.citation: N Engl J Med. 2007 Mar 29;356(13):1317-26
references.pmid: 17392301
references.citation: N Engl J Med. 2014 May 29;370(22):2071-82
references.pmid: 24836310
references.citation: Stem Cells. 2014 Feb;32(2):402-13
references.pmid: 24123810
references.citation: Am J Respir Crit Care Med. 2015 Mar 15;191(6):646-55
references.pmid: 25607374
references.citation: Cell. 2013 May 9;153(4):910-8
references.pmid: 23643243
references.citation: Lancet. 2011 Dec 3;378(9807):1949-61
references.pmid: 21719092
references.citation: Am J Hum Genet. 2009 Jan;84(1):52-9
references.pmid: 19100526
references.citation: Am J Physiol Lung Cell Mol Physiol. 2012 Apr 15;302(8):L721-9
references.pmid: 22287606
references.citation: Science. 2014 Jan 31;343(6170):506-11
references.pmid: 24482476
references.citation: Free Radic Biol Med. 2008 Mar 15;44(6):1097-107
references.pmid: 18206657
references.citation: Eur Respir J. 2007 Jan;29(1):134-7
references.pmid: 17005585
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1191-8
references.pmid: 11076809
references.citation: BMJ Open Respir Res. 2014 Dec 10;1(1):e000057
references.pmid: 25553246
references.citation: Am J Respir Crit Care Med. 2013 Dec 15;188(12):1442-50
references.pmid: 24070541
references.citation: Am J Respir Cell Mol Biol. 2012 Sep;47(3):324-31
references.pmid: 22461427
references.citation: Respir Res. 2012;13:64
references.pmid: 22853774
references.citation: Am J Med. 1965 Sep;39:411-21
references.pmid: 14338292
references.citation: Am J Respir Crit Care Med. 2015 Feb 15;191(4):417-26
references.pmid: 25389906
references.citation: Eur J Hum Genet. 2015 Sep;23(9):1124-8
references.pmid: 25564039
references.citation: Eur Respir J. 2011 Oct;38(4):861-9
references.pmid: 21828032
references.citation: Am J Respir Crit Care Med. 2008 Oct 15;178(8):838-46
references.pmid: 18635891
references.citation: Thorax. 2013 May;68(5):436-41
references.pmid: 23321605
references.citation: Trends Cell Biol. 2014 Jul;24(7):416-25
references.pmid: 24582487
references.citation: Mol Biol Cell. 2012 Jul;23(14):2782-92
references.pmid: 22593209
references.citation: Am J Respir Crit Care Med. 2005 Nov 1;172(9):1146-52
references.pmid: 16109978
references.citation: Am J Public Health. 2013 Oct;103 Suppl 1:S133-5
references.pmid: 23927510
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7
references.pmid: 17460043
references.citation: FASEB J. 2010 Apr;24(4):1167-77
references.pmid: 19966137
references.citation: Lancet Respir Med. 2014 Jul;2(7):557-65
references.pmid: 24948432
references.citation: J Biol Chem. 2011 Sep 2;286(35):30972-80
references.pmid: 21757695
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L720-9
references.pmid: 17586700
references.citation: JAMA. 2013 Jun 5;309(21):2232-9
references.pmid: 23695349
references.citation: Respir Med. 2011 Dec;105(12):1902-7
references.pmid: 21917441
references.citation: J Med Genet. 2008 Oct;45(10):654-6
references.pmid: 18835860
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Suppl):S47-50
references.pmid: 14503554
references.citation: Int J Chron Obstruct Pulmon Dis. 2011;6:309-19
references.pmid: 21697995
references.citation: Am J Respir Crit Care Med. 2010 Dec 1;182(11):1419-25
references.pmid: 20656946
references.citation: Eur Respir J. 2014 Jul;44(1):269-70
references.pmid: 24982060
references.citation: J Virol. 2005 Jun;79(11):6890-9
references.pmid: 15890928
references.citation: Am J Physiol Lung Cell Mol Physiol. 2009 Jan;296(1):L57-70
references.pmid: 18952756
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10562-7
references.pmid: 21670280
references.citation: Am J Respir Cell Mol Biol. 2005 Jun;32(6):521-30
references.pmid: 15778495
references.citation: Chest. 2010 Apr;137(4):969-73
references.pmid: 20371530
references.citation: N Engl J Med. 2013 Jun 6;368(23):2192-200
references.pmid: 23692170
references.citation: PLoS One. 2011;6(2):e14715
references.pmid: 21373184
references.citation: Science. 2013 Oct 11;342(6155):239-42
references.pmid: 24115439
references.citation: Am J Physiol Lung Cell Mol Physiol. 2015 Jan 1;308(1):L33-47
references.pmid: 25344067
references.citation: J Neurol Neurosurg Psychiatry. 2014 May;85(5):478-85
references.pmid: 23833266
references.citation: Transl Res. 2014 May;163(5):494-502
references.pmid: 24434656
references.citation: Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37
references.pmid: 18635888
references.citation: Nat Rev Genet. 2011 Nov;12(11):745-55
references.pmid: 21946919
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13051-6
references.pmid: 18753630
references.citation: PLoS One. 2013;8(8):e70621
references.pmid: 23940607
references.citation: N Engl J Med. 2011 Apr 21;364(16):1503-12
references.pmid: 21506741
references.citation: Int J Biochem Cell Biol. 2012 Jan;44(1):101-12
references.pmid: 22016030
references.citation: Am J Respir Crit Care Med. 2002 May 1;165(9):1322-8
references.pmid: 11991887
references.citation: J Biol Chem. 2003 Dec 26;278(52):52739-46
references.pmid: 14525980
references.citation: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):755-8
references.pmid: 10934117
references.citation: Genet Med. 2015 Feb;17(2):131-42
references.pmid: 25058500
references.citation: PLoS One. 2010;5(5):e10680
references.pmid: 20502709
references.citation: Am J Respir Crit Care Med. 2011 Oct 15;184(8):904-12
references.pmid: 21757622