title: Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a devastating disease that probably involves several genetic loci. Several rare genetic variants and one common single nucleotide polymorphism (SNP) of MUC5B have been associated with the disease. Our aim was to identify additional common variants associated with susceptibility and ultimately mortality in IPF.
  
  
  METHODS
  First, we did a three-stage genome-wide association study (GWAS): stage one was a discovery GWAS; and stages two and three were independent case-control studies. DNA samples from European-American patients with IPF meeting standard criteria were obtained from several US centres for each stage. Data for European-American control individuals for stage one were gathered from the database of genotypes and phenotypes; additional control individuals were recruited at the University of Pittsburgh to increase the number. For controls in stages two and three, we gathered data for additional sex-matched European-American control individuals who had been recruited in another study. DNA samples from patients and from control individuals were genotyped to identify SNPs associated with IPF. SNPs identified in stage one were carried forward to stage two, and those that achieved genome-wide significance (p<5 × 10(-8)) in a meta-analysis were carried forward to stage three. Three case series with follow-up data were selected from stages one and two of the GWAS using samples with follow-up data. Mortality analyses were done in these case series to assess the SNPs associated with IPF that had achieved genome-wide significance in the meta-analysis of stages one and two. Finally, we obtained gene-expression profiling data for lungs of patients with IPF from the Lung Genomics Research Consortium and analysed correlation with SNP genotypes.
  
  
  RESULTS
  In stage one of the GWAS (542 patients with IPF, 542 control individuals matched one-by-one to cases by genetic ancestry estimates), we identified 20 loci. Six SNPs reached genome-wide significance in stage two (544 patients, 687 control individuals): three TOLLIP SNPs (rs111521887, rs5743894, rs5743890) and one MUC5B SNP (rs35705950) at 11p15.5; one MDGA2 SNP (rs7144383) at 14q21.3; and one SPPL2C SNP (rs17690703) at 17q21.31. Stage three (324 patients, 702 control individuals) confirmed the associations for all these SNPs, except for rs7144383. Linkage disequilibrium between the MUC5B SNP (rs35705950) and TOLLIP SNPs (rs111521887 [r(2)=0·07], rs5743894 [r(2)=0·16], and rs5743890 [r(2)=0·01]) was low. 683 patients from the GWAS were included in the mortality analysis. Individuals who developed IPF despite having the protective TOLLIP minor allele of rs5743890 carried an increased mortality risk (meta-analysis with fixed-effect model: hazard ratio 1·72 [95% CI 1·24-2·38]; p=0·0012). TOLLIP expression was decreased by 20% in individuals carrying the minor allele of rs5743890 (p=0·097), 40% in those with the minor allele of rs111521887 (p=3·0 × 10(-4)), and 50% in those with the minor allele of rs5743894 (p=2·93 × 10(-5)) compared with homozygous carriers of common alleles for these SNPs.
  
  
  CONCLUSIONS
  Novel variants in TOLLIP and SPPL2C are associated with IPF susceptibility. One novel variant of TOLLIP, rs5743890, is also associated with mortality. These associations and the reduced expression of TOLLIP in patients with IPF who carry TOLLIP SNPs emphasise the importance of this gene in the disease.
  
  
  BACKGROUND
  National Institutes of Health; National Heart, Lung, and Blood Institute; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis; and Instituto de Salud Carlos III.
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Imre
authors.initials: I
authors.lastname: Noth
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Shwu-Fan
authors.initials: SF
authors.lastname: Ma
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Mathew
authors.initials: M
authors.lastname: Barber
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Steven M
authors.initials: SM
authors.lastname: Broderick
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wade
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Pirro
authors.initials: P
authors.lastname: Hysi
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Joseph
authors.initials: J
authors.lastname: Scuirba
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Richards
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Juan-Guardela
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Rekha
authors.initials: R
authors.lastname: Vij
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: MeiLan K
authors.initials: MK
authors.lastname: Han
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Karl
authors.initials: K
authors.lastname: Kossen
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Seiwert
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Dan
authors.initials: D
authors.lastname: Nicolae
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.affiliation: Section of Pulmonary and Critical Care Medicine (Prof I Noth MD, S-F Ma PhD, M Barber PhD, Y Huang MS, S M Broderick BS, R Vij MD) and Section of Genetic Medicine (Prof D Nicolae PhD), University of Chicago, Chicago, IL, USA; Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Y Zhang PhD, J Scuirba BS, T J Richards PhD, B M Juan-Guardela MD, Prof N Kaminski MD); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain (C Flores PhD); Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain (C Flores); Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, IL, USA (M S Wade MS, Prof J G N Garcia MD); Department of Twin Research and Genetic Epidemiology, King's College London, London, UK (P Hysi PhD); Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA (M K Han MD, Prof F J Martinez MD); InterMune, Brisbane, CA, USA (K Kossen PhD, S D Seiwert PhD); and Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Pennsylvania, PA, USA (J D Christie MD).
authors.forename: Joe G N
authors.initials: JGN
authors.lastname: Garcia
mesh_terms: D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000401:mortality; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D004247:DNA