{
  "abstract": "Objective The common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.Methods Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their association in a meta-analysis to increase the consistency of the results, including 10 European ancestry cohorts comprising 2363 patients with SSc-ILD, 3526 SSc patients without ILD and 15 076 controls.Results Meta-analysis showed no significant association between rs35705950 and SSc-ILD, either comparing patients with SSc with and without ILD (p value: 0.588, OR: 1.05, 95% CI: 0.87 to 1.27) nor patients with SSc-ILD with controls (p value: 0.061, OR: 1.16, 95% CI: 0.99 to 1.36). Moreover, none of the additional 903 variants tested in the genomic region reached statistical significance.Conclusion Despite analysing the largest and most statistically powered SSc-ILD cohort to date, we found no evidence of association between the MUC5B promoter variant rs35705950 and its surrounding SNPs with SSc-ILD. These results suggest that the pathogenic mechanisms underlying SSc-ILD may only partially overlap with those of other similar ILDs, such as IPF or RA-ILD. This highlights the need for further studies regarding their genetic architecture.",
  "authors": [
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Carlos Rosa-Baez"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Carlos Rangel-Pelaez"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Inmaculada Rodriguez-Martin"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Martin Kerick"
    },
    {
      "affiliations": [
        "Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Alfredo Guillen-Del-Castillo"
    },
    {
      "affiliations": [
        "Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Carmen P Simeon-Aznar"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Hospital San Cecilio, Granada, Spain"
      ],
      "name": "José Luis Callejas"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam UMC, Amsterdam, Netherlands"
      ],
      "name": "Alexandre E Voskuyl"
    },
    {
      "affiliations": [
        "Department of Dermatology, Venereology, and Allergology, Helios St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Oberhausen, Germany"
      ],
      "name": "Alexander Kreuter"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zürich Center of Experimental Rheumatology, Zürich, Switzerland"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Royal Adelaide Hospital and University of Adelaide, Adelaide, Victoria, Australia"
      ],
      "name": "Susanna M Proudman"
    },
    {
      "affiliations": [
        "University of Sydney School of Public Health, Royal Prince Alfred Hospital Sydney, and Sydney MSK Research Flagship Centre, University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Mandana Nikpour"
    },
    {
      "affiliations": [
        "Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany"
      ],
      "name": "Nicolas Hunzelmann"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"
      ],
      "name": "Jeska K De Vries-Bouwstra"
    },
    {
      "affiliations": [
        "Centre for Musculoskeletal Research, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"
      ],
      "name": "Ariane L Herrick"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Université Paris Cité UFR de Médecine, Paris, France"
      ],
      "name": "Yannick Allanore"
    },
    {
      "affiliations": [
        "Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy"
      ],
      "name": "Lorenzo Beretta"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of internal medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA"
      ],
      "name": "Maureen D Mayes"
    },
    {
      "affiliations": [
        "Division of Medicine, University College London, London, UK"
      ],
      "name": "Christopher P Denton"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of internal medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA"
      ],
      "name": "Shervin Assassi"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Javier Martin"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"
      ],
      "name": "Marialbert Acosta-Herrera"
    },
    {
      "affiliations": [
        "Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain",
        "Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d’Hebron, Barcelona, Spain",
        "Department of Internal Medicine, Hospital San Cecilio, Granada, Spain",
        "Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam UMC, Amsterdam, Netherlands",
        "Department of Dermatology, Venereology, and Allergology, Helios St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Oberhausen, Germany",
        "Department of Rheumatology, University Hospital Zürich Center of Experimental Rheumatology, Zürich, Switzerland",
        "Rheumatology Unit, Royal Adelaide Hospital and University of Adelaide, Adelaide, Victoria, Australia",
        "University of Sydney School of Public Health, Royal Prince Alfred Hospital Sydney, and Sydney MSK Research Flagship Centre, University of Sydney, Sydney, New South Wales, Australia",
        "Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany",
        "Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands",
        "Centre for Musculoskeletal Research, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK",
        "Department of Rheumatology, Université Paris Cité UFR de Médecine, Paris, France",
        "Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy",
        "Division of Rheumatology, Department of internal medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA",
        "Division of Medicine, University College London, London, UK"
      ],
      "name": "International SSc Group"
    },
    {
      "affiliations": [],
      "name": "Australian Scleroderma Interest Group (ASIG)"
    }
  ],
  "title": "Assessing the MUC5B promoter variant in a large cohort of systemic sclerosis-associated interstitial lung disease",
  "uid": "ea2cc315-69b0-5ef3-a9f8-255537c8c500"
}