A Novel Index of Early-life Growth Conditions Moderates Susceptibility to Later-life Cigarette Smoking-associated Airflow Obstruction and Systemic Inflammation
Bibliographic record
Abstract
Abstract Rationale: Early-life growth conditions and later-life cigarette smoking are major pathways to chronic obstructive pulmonary disease (COPD), but whether these factors interact is poorly understood. Attained height is determined in part by early-life growth conditions and by genetics, and the difference between attained and genotype-predicted height (height-GaP) is a prospectively validated index of early-life growth conditions. This study sought to investigate whether height-GaP moderates susceptibility to cigarette smoking-associated airflow obstruction and systemic inflammation. Methods: UKBiobank is cohort of community-dwelling adults 40-69 years old at enrolment. Participants completed standardised assessments of anthropometry, smoking behaviours, genotyping, spirometry and serum C-reactive protein concentration (CRP). Genotype-predicted height was calculated using a polygenic height score derived from individual genotype data. Airflow obstruction was defined using pre-bronchodilator FEV1/FVC <0.70. Regression models of airflow obstruction prevalence and CRP were fit with 10+ pack-years and current smoking status as the respective independent variables of interest. Moderation of these associations by height-GaP were assessed by including a height-GaP product term in each model and were additionally adjusted for age, age2, sex, principal components of genetic ancestry, and genotype-predicted height. Results: Among 293,018 adults with quality-verified spirometry, height, genotype and pack-year data (mean±SD age 56±8 years, 54.2% female, 27.4% smoked 10+ pack-years, 15.9% airflow obstruction prevalence), 10+ pack-years of cigarette smoking was associated with 10.3% excess airflow obstruction prevalence, but this association varied with height-GaP (p-interaction=4.35e-06). Smoking 10+ pack-years in the lowest height-GaP quintile (i.e., largest height deficit) was associated with 12.2% excess airflow obstruction prevalence compared to 8.7% excess airflow obstruction prevalence in the highest height-GaP quintile (Figure 1a) – a +40% relative excess of airflow obstruction prevalence. Among 461,108 adults with serum CRP, height, genotype and smoking status data (mean±SD age 56±8 years, 54.2% female, 10.5% current smokers, median (IQR) serum CRP 1.33 (0.66-2.76) mg/L), current smoking was associated with +0.84 mg/L higher CRP concentration, but this association varied with height-GaP (p-interaction=1.05e-12). Current smoking in the lowest height-GaP quintile (i.e., largest height deficit) was associated with +1.06 mg/L higher CRP concentration compared to +0.62 mg/L higher CRP in the highest quintile – a +70% relative increment in serum CRP concentration (Figure 1b). Conclusion: Early-life growth conditions, quantified as the difference between attained height and genotype-predicted height, appear to moderate susceptibility to cigarette smoking-associated airflow obstruction and systemic inflammation. These findings suggest that early-life conditions that affect growth may alter later-life susceptibility to pro-inflammatory stimuli and associated health outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".