{
  "abstract": "Rationale At least half of chronic obstructive pulmonary disease (COPD) occurs in individuals with subnormal preceding lung function trajectory. Identifying which early-life phenotypes causally influence risk of adverse trajectories could facilitate disease prevention. Objectives Using Mendelian randomization (MR), we investigated whether previous early-life phenotypic associations with lower trajectories are compatible with a causal effect. Methods Outcomes were lower FEV1 trajectory groups from latent profile analysis in participants with [≥]2 measurements at ages 8, 15, 24 or 30 in the Avon Longitudinal Study of Parents and Children (% predicted; n=5,165). Nine exposures were prioritized for MR from observational associations with lower trajectories in logistic regression. Two-stage residual inclusion MR, applying polygenic risk scores of variants from the largest published genome-wide association studies, estimated genetically instrumented effects of exposures on odds of lower trajectories. Results Of five trajectories identified, two had lower mean FEV1: Below Average (87.7% predicted) and Persistently Low (72.6% predicted). Observationally, higher birth weight and childhood body mass index (BMI) were associated with lower odds of these trajectories, and pre-school wheeze, childhood aeroallergen sensitization, asthma and airways hyperresponsiveness with higher odds. MR evidence suggested childhood-onset asthma causally increased odds of lower trajectories (OR 9.62; 95% CI 1.49-119.7). MR estimates were directionally concordant with observational analyses but with confidence intervals crossing null for birth weight and aeroallergen sensitization, and were near-null for BMI. Conclusions These findings support a causal role for childhood-onset asthma in subnormal lung function trajectories, suggesting its optimized diagnosis and management as targets for COPD prevention.",
  "abstract_shown": true,
  "affiliations": [
    "University of Bristol"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. S. Grenville"
    },
    {
      "name": "R. C. Richmond"
    },
    {
      "name": "G. M. Power"
    },
    {
      "name": "P. D. Yousefi"
    },
    {
      "name": "J. W. Dodd"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7mf1t00ywc7en.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.26366597",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.27.26366597v1.full",
  "id": "7mf1t00ywc7en",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.27.26366597v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "epidemiology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.27.26366597v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7mf1t00ywc7en.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:03Z",
      "native_id": "10.64898/2026.10.27.26366597",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.27.26366597v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:epidemiology",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Causal effects of early-life traits on lung function trajectory: a Mendelian randomization study",
  "title_text": "Causal effects of early-life traits on lung function trajectory: a Mendelian randomization study",
  "type": "preprint",
  "updated_at": "2026-11-01T00:20:31Z",
  "url": "https://research.draconitic.com/paper/7mf1t00ywc7en",
  "venue": "medRxiv",
  "versions": []
}