title: Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients.
abstract: BACKGROUND
  Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc.
  
  
  METHODS
  A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc.
  
  
  RESULTS
  We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort.
  
  
  CONCLUSIONS
  Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Minghua.wu@uth.tmc.edu.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Shervin.assassi@uth.tmc.edu.
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Gloria.SalazarCintora@uth.tmc.edu.
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Salazar
authors.affiliation: Department of Pediatrics, The University of Texas Mcgovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Claudia.Pedroza@uth.tmc.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pedroza
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH, 03755, USA. Olga.Y.Gorlova@dartmouth.edu.
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Gorlova
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH, 03755, USA. vwchen001@gmail.com.
authors.forename: Wei V
authors.initials: WV
authors.lastname: Chen
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Julio.Charles@uth.tmc.edu.
authors.forename: Julio
authors.initials: J
authors.lastname: Charles
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. miranda.l.taing@uth.tmc.edu.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Taing
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Kelley.Liao@uth.tmc.edu.
authors.forename: Kelley
authors.initials: K
authors.lastname: Liao
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. fwig@jhmi.edu.
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. lhummers@jhmi.edu.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Hummers
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. Ami.Shah@jhmi.edu.
authors.forename: Ami A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL, 60611, USA. m-hinchcliff@northwestern.edu.
authors.forename: Monique
authors.initials: M
authors.lastname: Hinchcliff
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. khannad@med.umich.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. eschiopu@med.umich.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Schiopu
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. kphill@med.umich.edu.
authors.forename: Kristine
authors.initials: K
authors.lastname: Phillips
authors.affiliation: Division of Rheumatology, University of California Los Angeles, 1000 Veterans Avenue, Los Angeles, CA, 90024, USA. DEFurst@mednet.ucla.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Division of Rheumatology, Georgetown University Medical Center, 3800 Reservoir Road, Washington, MD, 20007, USA. steenv@georgetown.edu.
authors.forename: Virginia
authors.initials: V
authors.lastname: Steen
authors.affiliation: Division of Rheumatology, McGill University, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. murray.baron@jgh.mcgill.ca.
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.affiliation: Division of Rheumatology, McGill University, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. marie.hudson@mcgill.ca.
authors.forename: Marie
authors.initials: M
authors.lastname: Hudson
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. xiaodong.zhou@uth.tmc.edu.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Division of Rheumatology, St. Joseph's Health Care, University of Western Ontario, 268 Grosvenor Street, London, ON, Canada. janet.pope@sjhc.london.on.ca.
authors.forename: Janet
authors.initials: J
authors.lastname: Pope
authors.affiliation: Division of Rheumatology, University of Alberta, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada. sameitjones@shaw.ca.
authors.forename: Niall
authors.initials: N
authors.lastname: Jones
authors.affiliation: Division of Rheumatology, Moncton Hospital, 135 MacBeath Avenue, Moncton, NB, E1C 6Z8, Canada. pedocher@serha.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Docherty
authors.affiliation: Division of Rheumatology, McMaster University at Hamilton, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada. naderkhalidi@sympatico.ca.
authors.forename: Nader A
authors.initials: NA
authors.lastname: Khalidi
authors.affiliation: Division of Rheumatology, University of Manitoba, 820 Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada. drobinson@hsc.mb.ca.
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Division of Rheumatology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. rsimms@bu.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simms
authors.affiliation: Division of Rheumatology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, 29425, USA. silverr@musc.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver
authors.affiliation: Division of Rheumatology, University of Utah, 30 North 1900 East, Salt Lake City, UT, 84132, USA. Tracy.frech@hsc.utah.edu.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Frech
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AB, 35294, USA. bjf@uab.edu.
authors.forename: Barri J
authors.initials: BJ
authors.lastname: Fessler
authors.affiliation: Division of Rheumatology, University of Calgary Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. fritzler@ucalgary.ca.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.affiliation: Division of Rheumatology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. jmolitor@umn.edu.
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Molitor
authors.affiliation: Division of Rheumatology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. Segal017@umn.edu.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Segal
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Malahat.Movahedian@uth.tmc.edu.
authors.forename: Malahat
authors.initials: M
authors.lastname: Movahedian
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Cientıficas, C/Ventanilla 11, 18001, Granada, Spain. martin@ipb.csic.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL, 60611, USA. j-varga@northwetern.edu.
authors.forename: John
authors.initials: J
authors.lastname: Varga
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Maureen.D.Mayes@uth.tmc.edu.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000235:genetics*; D044465:White People / Q000235:genetics*