{
  "abstract": "Background The association between lower adult lung function and increased cardiovascular comorbidity has not been adequately explained. We investigated whether shared developmental signalling pathways, critical to lung development and repair, could partly explain it.Methods In UK Biobank (UKB), we performed pairwise colocalisation analysis of variants in 55 lung development genes associated with adult forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV 1)/FVC, to see if these are also associated with coronary heart disease (CHD), blood pressure (systolic, diastolic, hypertension), pulse pressure, Arterial Stiffness index and carotid intima-media thickness. For CHD, we meta-analysed data from UKB and the CARDIoGRAM consortium.Results We found that 12 of the 55 genes shared the same variant between one (or more) lung function trait and one (or more) cardiovascular trait (H4colocalisation). The direction of effects was always in keeping with our hypothesis (lower lung function–higher cardiovascular risk) for FVC, but not always for FEV 1/FVC. The seven signals for hypertension and CHD all replicated nominally in the FinnGen study, while replication was poor in the China Kadoorie Biobank (CKB) study. In addition, we found a further 10 genes where genetic associations with lung function and cardiovascular traits were within the same gene but involved different variants (H3 colocalisation). Interestingly, six of all 22 genes (H4 and H3 colocalisation) were novel for cardiovascular traits; four replicated in FinnGen, three in CKB.Conclusion Lung function and cardiovascular traits have shared developmental pathways that may partly explain why lower lung function, especially FVC, is associated with increased cardiovascular risk.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK",
        "Nuffield Department of Population Health, University of Oxford, Oxford, UK",
        "Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK"
      ],
      "name": "Laura Portas"
    },
    {
      "affiliations": [
        "Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"
      ],
      "name": "Mohammad Talaei"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Division of Respiratory Science, London, UK"
      ],
      "name": "Charlotte Dean"
    },
    {
      "affiliations": [
        "Barts and The London School of Medicine and Dentistry William Harvey Research Institute, London, UK",
        "Saint Bartholomew’s Hospital Barts Heart Centre, London, UK"
      ],
      "name": "Nay Aung"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK",
        "Respiratory Medicine, Royal Brompton Hosital, London, UK"
      ],
      "name": "Matthew David Hind"
    },
    {
      "affiliations": [
        "Nuffield Department of Population Health, University of Oxford, Oxford, UK"
      ],
      "name": "Alfred Pozarickij"
    },
    {
      "affiliations": [
        "Nuffield Department of Population Health, University of Oxford, Oxford, UK"
      ],
      "name": "Robin G Walters"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK",
        "Nuffield Department of Population Health, University of Oxford, Oxford, UK",
        "Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK",
        "Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK",
        "National Heart and Lung Institute, Division of Respiratory Science, London, UK",
        "Barts and The London School of Medicine and Dentistry William Harvey Research Institute, London, UK",
        "Saint Bartholomew’s Hospital Barts Heart Centre, London, UK",
        "Respiratory Medicine, Royal Brompton Hosital, London, UK",
        "Centre for Advanced Cardiovascular Imaging, Barts and The London School of Medicine an Dentistry, London, UK"
      ],
      "name": "China Kadoorie Biobank Collaborative Group"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Peter GJ Burney"
    },
    {
      "affiliations": [
        "Centre for Advanced Cardiovascular Imaging, Barts and The London School of Medicine an Dentistry, London, UK"
      ],
      "name": "Steffen Petersen"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Cosetta Minelli"
    },
    {
      "affiliations": [
        "Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"
      ],
      "name": "Seif O Shaheen"
    }
  ],
  "title": "Lung development genes, adult lung function and cardiovascular comorbidities",
  "uid": "47fe28c3-906d-59b4-a5a7-12f4471fdfd6"
}