SynthesisPLoS genetics2021
Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.
Synthesis in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Sexually Dimorphic Neuroimmune Pathways in Chronic Pain: A Comprehensive Systematic Review of Cellular and Molecular Mechanisms.Biomolecules · 2026Pooled it
- A multi-ancestry genetic study of pain intensity in 598,339 veterans.Nature medicine · 2024Pooled it
- Genome wide association joint analysis reveals 99 risk loci for pain susceptibility and pleiotropic relationships with psychiatric, metabolic, and immunological traits.PLoS genetics · 2023Pooled it
- Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility.JAMA network open · 2021Pooled it
- Disentangling the association between chronic pain and sarcopenia-related traits: A bidirectional Mendelian randomization study.The Journal of international medical research · 2026Article
- Genotype-dependent miR-499/SOX5 axis regulation and its association with chronic low back pain risk and severity.Journal of orthopaedic surgery and research · 2026Article
- Dopamine transporter gene (Pain reports · 2026Article
- The genetics of fibromyalgia and its relationships to psychiatric and medical traits.Nature communications · 2026Article
- Adolescent pain reports share genetic overlap with adult chronic pain conditions: A polygenic score analysis using the ABCD study.The journal of pain · 2026Article
- GWAS of extended prescription analgesic use identifies genetic loci in chronic pain.Nature communications · 2026Article
- Review
- Single-cell multi-omics sequencing reveals cell-specific transcriptomic and chromatin accessibility profiles in gut microbiome metabolite butyrate-produced pain modulation.International journal of oral science · 2026Article
- Concordance of cortical morphological anomalies with genetic predisposition to multisite chronic pain in females.The Korean journal of pain · 2026Article
- Causal evidence linking chronic pain genetics to late-onset asthma via the nervous system.British journal of anaesthesia · 2026Article
- Functional expression of the T-type Cav3.2 calcium channel in female and male human dorsal root ganglion neurons.Brain : a journal of neurology · 2026Article
- Association Between Long-Term ACEI/ARB Use and Postoperative Pain in Hypertensive Patients: A Retrospective Cohort Study and Genetic Validation.Journal of pain research · 2026Article
- The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.The Journal of clinical investigation · 2025Article
- Genetic underpinnings and causal effects of brain structure and function on chronic pain intensity.Nature communications · 2025Article
- Review
- Concordance between male- and female-specific GWAS results helps define underlying genetic architecture of complex traits.Nature communications · 2025Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.