Multisite chronic pain as a causal risk factor for coronary artery disease: findings from Mendelian randomization

Zhu, Jiahao; Wang, Nini; Liu, Houpu; Jiang, Han; Cai, Bingyue; Chen, Dingwan; Li, Yingjun

doi:10.1097/j.pain.0000000000002732

Cited by 12 publications

(9 citation statements)

References 63 publications

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“…Our results are consistent with earlier MR studies that have shown positive causal effects of BMI and smoking on RA/MS, and positive causal effects of MCP on BMI and smoking initiation ( 5 , 48 – 50 ). Together, these findings provided support for BMI and smoking as causative mediators (mechanisms) linking a larger number of chronic pain sites to an increased risk of developing MS/RA.…”

Section: Discussionsupporting

confidence: 93%

“…In the second step, SNPs for potential mediating risk variables were utilized to genetically predict these mediators and assess their causal effect on the AIDs. For MR mediation analysis, potential mediators which presented supporting evidence for two stages in MR (causal effects of MCP on mediators and causal effects of mediators on AIDs) were considered (5). The entire effect of MCP on AIDs as assessed by MR can be split into direct (not mediated by mediators) and indirect effects (effect mediated by the mediators).…”

Section: Two-step Mr and Mediation Analysismentioning

confidence: 99%

“…Around 30% of the global population suffers from chronic pain, with an average of three pain locations reported ( 3 ). Multisite chronic pain (MCP) and chronic widespread pain (CWP), as a derived chronic pain phenotype, are widely spread among the older population ( 4 , 5 ). The global prevalence of CWP in the general population ranged from 10.6% to 11.8% ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…In rheumatoid arthritis (RA), the frequent disconnect between pain and inflammation is an unexplained aspect of chronic pain. Joint pain often precedes evidence of joint inflammation and is therefore also considered to be one of the early signs of emerging RA ( 5 ). Moreover, duo to pain connected to developing psoriasis, long-term acetaminophen and NSAIDs use may be associated with an increased risk of psoriasis ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Tang

Liu²,

Kong³

et al. 2023

Front. Immunol.

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BackgroundAccumulating evidence has demonstrated that an association between chronic pain and autoimmune diseases (AIDs). Nevertheless, it is unclear whether these associations refer to a causal relationship. We used a two-sample Mendelian randomization (MR) method to determine the causal relationship between chronic pain and AIDs.MethodsWe assessed genome-wide association study (GWAS) summary statistics for chronic pain [multisite chronic pain (MCP) and chronic widespread pain (CWP)], and eight common AIDs, namely, amyotrophic lateral sclerosis (ALS), celiac disease (CeD), inflammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), type 1 diabetes (T1D) and psoriasis. Summary statistics data were from publicly available and relatively large-scale GWAS meta-analyses to date. The two-sample MR analyses were first performed to identify the causal effect of chronic pain on AIDs. The two-step MR and multivariable MR were used to determine if mediators (BMI and smoking) causally mediated any connection and to estimate the proportion of the association mediated by these factors combined.ResultsWith the utilization of MR analysis, multisite chronic pain was associated with a higher risk of MS [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.49, P = 0.044] and RA (OR = 1.72, 95% CI = 1.06-2.77, P = 0.028). However, multisite chronic pain had no significant effect on ALS (OR = 1.26, 95% CI = 0.92-1.71, P = 0.150), CeD (OR = 0.24, 95% CI = 0.02-3.64, P = 0.303), IBD (OR = 0.46, 95% CI = 0.09-2.27, P = 0.338), SLE (OR = 1.78, 95% CI = 0.82-3.88, P = 0.144), T1D (OR = 1.15, 95% CI = 0.65-2.02, P = 0.627) or Psoriasis (OR = 1.59, 95% CI = 0.22-11.26, P = 0.644). We also found positive causal effects of MCP on BMI and causal effects of BMI on MS and RA. Moreover, there were no causal connections between genetically predicted chronic widespread pain and the risk of most types of AIDs disease.ConclusionOur MR analysis implied a causal relationship between MCP and MS/RA, and the effect of MCP on MS and RA may be partially mediated by BMI.

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Section: Discussionsupporting

confidence: 93%

Section: Two-step Mr and Mediation Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Tang

Liu²,

Kong³

et al. 2023

Front. Immunol.

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“…Even though a considerably high prevalence rate was observed, the overlapping nature of pain conditions was frequently neglected in previous studies. Multiple lines of evidence have suggested that MCP relates to extra burdens on psychiatric, autoimmune, and anthropometric traits ( 20 ); risk of coronary artery disease ( 21 ); axonogenesis in the hippocampal limbic system ( 18 ); and quality of life ( 22 ), most of which were key factors that aggravate cognitive impairment and dementia progression ( 23 – 32 ). Nevertheless, whether and to what extent MCP is associated with dementia risk and cognitive decline, compared to both PF and single-site CP (SCP), is unknown.…”

mentioning

confidence: 99%

Elevated dementia risk, cognitive decline, and hippocampal atrophy in multisite chronic pain

Zhao

Chang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Numerous studies have investigated the impacts of common types of chronic pain (CP) on patients’ cognitive function and observed that CP was associated with later dementia. More recently, there is a growing recognition that CP conditions frequently coexist at multiple body sites and may bring more burdens on patients’ overall health. However, whether and how multisite CP (MCP) contributes to an increased risk of dementia, compared to single-site CP (SCP) and pain-free (PF), is largely unclear. In the current study, utilizing the UK Biobank cohort, we first investigated dementia risk in individuals (n = 354,943) with different numbers of coexisting CP sites using Cox proportional hazards regression models. We then applied generalized additive models to investigate whether MCP leads to excessive deterioration of participants’ (n = 19,116) cognition and brain structure. We found that individuals with MCP were associated with significantly higher dementia risk, broader and faster cognitive impairment, and greater hippocampal atrophy than both PF individuals and those with SCP. Moreover, the detrimental effects of MCP on dementia risk and hippocampal volume aggravated along with the number of coexisting CP sites. Mediation analyses further revealed that the decline of fluid intelligence in MCP individuals was partially mediated by hippocampal atrophy. Our results suggested that cognitive decline and hippocampal atrophy interact biologically and may underlie the increased risk of dementia associated with MCP.

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Genetic insights into associations of multisite chronic pain with common diseases and biomarkers using data from the UK Biobank

Chen,

Sun,

Wang

et al. 2024

British Journal of Anaesthesia

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Multisite chronic pain as a causal risk factor for coronary artery disease: findings from Mendelian randomization

Abstract: Supplemental Digital Content is Available in the Text.Multisite chronic pain has a causal effect on the risk of coronary artery disease, which is partly mediated through body mass index, smoking, and depression.

Cited by 12 publications

References 63 publications

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Elevated dementia risk, cognitive decline, and hippocampal atrophy in multisite chronic pain

Genetic insights into associations of multisite chronic pain with common diseases and biomarkers using data from the UK Biobank

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