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[Preprint]. 2024 May 8:2023.06.27.23291959.
doi: 10.1101/2023.06.27.23291959.

Chronic Overlapping Pain Conditions and Nociplastic Pain

Keira J A Johnston  1 , Rebecca Signer  2 , Laura M Huckins  1
Affiliations

Chronic Overlapping Pain Conditions and Nociplastic Pain

Keira J A Johnston et al. medRxiv. .

Update in

Abstract

Chronic Overlapping Pain Conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and assigned female at birth (AFAB) individuals. Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic type pain may represent a shared underlying factor among COPCs. We applied GenomicSEM common-factor genome wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic type pain, followed by genetic correlation (linkage-disequilibrium score regression), gene-set and tissue enrichment analyses. We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic type pain, and showed nociplastic type pain to be a polygenic trait with significant SNP-heritability. We found significant genetic overlap between multisite chronic pain and nociplastic type pain, and to a smaller extent with rheumatoid arthritis and a neuropathic pain phenotype. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic type pain along with distinct pathology in migraine and headache. We use a well-powered network approach to investigate nociplastic type pain using existing COPC GWAS output, and show nociplastic type pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Figures

Figure 1:
Figure 1:. Path diagram of common factor GWAS GenomicSEM model.
Values = Standardized Estimate (Standard Error).
Figure 2:
Figure 2:. Manhattan plot of nociplastic-type pain common-factor GWAS and multivariate TWAS outputs.
A: Nociplastic-type pain – common-factor GWAS Manhattan plot. Dotted line = genome-wide p value significance threshold (−log10(5 × 10−8)). B: Nociplastic-type pain – multivariate TWAS Manhattan plot. X-axis labels = GTEx v8 tissue, points shown in orange = gene-tissue associations significant after Bonferroni adjustment within that tissue, labeled points = genes with most significant association within that tissue.
Figure 3:
Figure 3:. GWAS catalog trait gene set enrichments.
A: Gene sets enriched for all nociplastic-type pain genes found in multivariate TWAS analysis, B: Gene sets enriched for specific nociplastic type pain genes, Panel C: Gene sets enriched for non-specific nociplastic type pain genes.
See this image and copyright information in PMC

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