| Title: | Causal evidence linking chronic pain genetics to late-onset asthma via the nervous system |
| Journal: | British Journal of Anaesthesia |
| Published: | 17 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41547614/ |
| DOI: | https://doi.org/10.1016/j.bja.2025.11.020 |
| URL: | https://www.bjanaesthesia.org/article/S0007-0912(25)00823-2/pdf |
Publication 18633
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Abstract
BACKGROUND: Chronic pain and asthma are associated, but the direction and basis of their genetic and biological relationship remain unclear.</p>
METHODS: We conducted genome-wide association studies (GWAS), multi-trait analysis of GWAS (MTAG), polygenic risk score (PRS) prediction, bivariate causal modelling, and Mendelian randomisation (MR) across nine chronic pain traits and three asthma age-of-onset strata (<18, 18-40, and >40 yr for childhood-, adult-, and late-onset asthma, respectively) in 456 958 UK Biobank and 25 275 Canadian Longitudinal Study on Aging participants of European descent. We analysed shared and distinct genetic architecture using gene-, pathway-, tissue-, and cell-type-based enrichment analyses.</p>
RESULTS: Multisite chronic pain (MCP) showed the strongest and most consistent genetic overlap with asthma, with genetic correlation increasing from childhood (rg=0.01) to late-onset asthma (rg=0.40). Estimated causal variants for late-onset asthma (∼1.8 K), and fewer for childhood asthma (∼0.2 K), were nested within a broader MCP profile (∼9.4 K). Using PRS, MR, and longitudinal analyses, we found that MCP contributes causally to late-onset asthma. Top causal variants from MR mapped to GMPPB-RNF123, DCC, and FOXP2. Conditioning by MCP amplified late-onset asthma variant effect sizes using MTAG, and uncovered genes enriched for immune and CNS function across pathways, tissues, and cell types. In contrast, childhood asthma showed immune-specific enrichment alone.</p>
CONCLUSIONS: These findings reveal neurological function linking chronic pain to late-onset asthma, distinct from childhood asthma, and highlight a CNS contribution to asthma emerging later in life.</p>
17 Keywords
- Adolescent
- Adult
- Age of Onset
- Aged
- Asthma
- Child
- Chronic Pain
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Longitudinal Studies
- Male
- Mendelian Randomization Analysis
- Middle Aged
- United Kingdom
- Young Adult
12 Authors
- Goodarz Kolifarhood
- Marc Parisien
- Matt Fillingim
- Charlise Chen
- Yiran Chen
- Nikolay Dimitrov
- Maha Zidan
- Lovéni Hanumunthadu
- Peter H. Her
- Sahir Bhatnagar
- Luda Diatchenko
- Audrey V. Grant
1 Application
| Application ID | Title |
|---|---|
| 20802 | A replication study of pain interactions with comorbidities |
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