| Title: | Genetic underpinnings and causal effects of brain structure and function on chronic pain intensity |
| Journal: | Nature Communications |
| Published: | 12 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41224763/ |
| DOI: | https://doi.org/10.1038/s41467-025-64904-y |
| URL: | https://www.nature.com/articles/s41467-025-64904-y.pdf |
Publication 18957
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Chronic pain represents a major clinical burden, with its intensity being a key measure of its severity. However, the genetic and neural underpinnings of chronic pain intensity remain unraveled. Here, we identified six genetic loci (including a novel discovery) significantly associated with chronic pain intensity using a genome-wide association study in the UK Biobank (n = 134,627). We then systematically investigate its relationship with 3924 brain imaging-derived phenotypes. Phenotypic correlation analyses revealed 29 imaging-derived phenotypes predictive of future chronic pain intensity. Genetic correlation and polygenic risk score analyses showed 13 of these imaging-derived phenotypes share a genetic basis with chronic pain intensity. Mediation analyses indicated that 12 imaging-derived phenotypes mediate genetic effects on chronic pain intensity. Mendelian randomization further supported a causal influence of three imaging-derived phenotypes, including brain structure and functional network connectivity, on chronic pain intensity. Our findings elucidate the genetic architecture and neurobiological pathways of chronic pain intensity, highlighting the brain's central role in chronic pain pathophysiology.</p>
17 Keywords
- Adult
- Aged
- Brain
- Chronic Pain
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Magnetic Resonance Imaging
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Multifactorial Inheritance
- Phenotype
- Polymorphism, Single Nucleotide
- United Kingdom
13 Authors
- Xiuzhi Wang
- Jinyu Liu
- Xichen Wang
- Jin Yang
- Yipeng Le
- Yingchao Song
- Qian Su
- Xiaoxiao Xiao
- Yifan Li
- Wen Qin
- Chunshui Yu
- Ping Wang
- Meng Liang
1 Application
| Application ID | Title |
|---|---|
| 75556 | Trans-ethnic genome-wide and exposome-wide association studies of neuroimaging and behavioral phenotypes |
Enabling scientific discoveries that improve human health