| Title: | Time from waking to first cigarette, genetic susceptibility, and the risk of COPD: A Prospective cohort study from UK Biobank |
| Journal: | Heart & Lung |
| Published: | 12 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41232450/ |
| DOI: | https://doi.org/10.1016/j.hrtlng.2025.11.005 |
Publication 18947
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Abstract
BACKGROUND: Smoking is a well-established risk factor for COPD, but the impact of time from waking to first cigarette (TWFC) remains underexplored, particularly regarding its interactions.</p>
OBJECTIVES: We aim to investigate the TWFC-COPD association among current smokers and evaluate its interactions with genetic susceptibility, smoking pack-years and difficulty not smoking for one day (DNSD).</p>
METHODS: Using data from 302,412 UK Biobank participants, a COPD genetic risk score (GRS) was developed from 22 independent established SNPs associated with COPD and related phenotypes. Cox proportional hazards models was used to estimate adjusted hazard ratios (aHRs, 95% CIs), and assesse additive and multiplicative interactions.</p>
RESULTS: Over a median follow-up of 12.42 years, 13,131 incident COPD cases were identified. Compared with never smokers, current smokers exhibited a significant inverse gradient association between shorter TWFC and increased COPD risk (P trend<0.001), with aHRs (95% CIs) increasing from 4.18 (3.66-4.78) for TWFC >120 min to 8.76 (8.01-9.58) for TWFC <5 min. Compared to current smokers with TWFC >120 min and low genetic risk, those with the shortest TWFC (<5 min) and high genetic risk had the highest COPD risk (aHR=2.85, 95% CI: 2.34-3.46), with a tendency toward additive interaction (RERI=0.26, 95% CI: -0.06-0.58; AP=8%, 95% CI: -0.03-0.19). Similarly, TWFC <5 min combined with higher pack-years (aHR=3.08, 95% CI: 2.66-3.57) or greater DNSD (aHR=5.14, 95% CI: 4.22-6.25) elevated the risk, with significant additive interactions.</p>
CONCLUSIONS: Shorter TWFC is strongly associated with increased COPD risk among current smokers, amplified by high genetic susceptibility to COPD, higher smoking pack-years, and greater DNSD.</p>
8 Authors
- Liu Qiqi
- Liu Haoxiang
- Wu Chuansha
- Sun Xiaojie
- Xiong Longzhu
- Kong Chunxue
- Ma Jixuan
- Zhou Ting
1 Application
| Application ID | Title |
|---|---|
| 88159 | Fine-mapping, genetic correlation and genetic risk prediction for complex traits in different populations |
Enabling scientific discoveries that improve human health