Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study

Williams, Frances; Elgaeva, Elizaveta E.; Freidin, Maxim B.; Zaytseva, Olga O.; Aulchenko, Yurii S.; Tsepilov, Yakov A.; Suri, Pradeep

doi:10.1007/s00586-022-07263-2

Cited by 18 publications

(20 citation statements)

References 38 publications

(30 reference statements)

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“…Of note, internalizing generally showed stronger associations with pain, general health, cardiovascular disease, and chronic illness than externalizing. Previous research also supports likely causal effects of genetic risk for internalizing traits/disorders on localized pain 90,91 and various disease outcomes. 92 An unexpected nding here was that internalizing was protective for IBD after removing pleiotropic variants.…”

Section: Discussionmentioning

confidence: 71%

A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra

Davis,

Khan,

Toikumo

et al. 2024

Preprint

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There is considerable comorbidity across externalizing and internalizing behavior dimensions of psychopathology. We applied genomic structural equation modeling (gSEM) to genome-wide association study (GWAS) summary statistics to evaluate the factor structure of externalizing and internalizing psychopathology across 16 traits and disorders among European-ancestry individuals (n’s = 16,400 to 1,074,629). We conducted GWAS on factors derived from well-fitting models. Downstream analyses served to identify biological mechanisms, explore drug repurposing targets, estimate genetic overlap between the externalizing and internalizing spectra, and evaluate causal effects of psychopathology liability on physical health. Both a correlated factors model, comprising two factors of externalizing and internalizing risk, and a higher-order single-factor model of genetic effects contributing to both spectra demonstrated acceptable fit. GWAS identified 409 lead single nucleotide polymorphisms (SNPs) associated with externalizing and 85 lead SNPs associated with internalizing, while the second-order GWAS identified 256 lead SNPs contributing to broad psychopathology risk. In bivariate causal mixture models, nearly all externalizing and internalizing causal variants overlapped, despite a genetic correlation of only 0.37 (SE = 0.02) between them. Externalizing genes showed cell-type specific expression in GABAergic, cortical, and hippocampal neurons, and internalizing genes were associated with reduced subcallosal cortical volume, providing insight into the neurobiological underpinnings of psychopathology. Genetic liability for externalizing, internalizing, and broad psychopathology exerted causal effects on pain, general health, cardiovascular diseases, and chronic illnesses. These findings underscore the complex genetic architecture of psychopathology, identify potential biological pathways for the externalizing and internalizing spectra, and highlight the physical health burden of psychiatric comorbidity.

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Section: Discussionmentioning

confidence: 71%

A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra

Davis,

Khan,

Toikumo

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…However, this link was not supported by sensitivity analyses using the weighted mode ( P = 0.281) and MR-Egger ( P = 0.228) methods. In 2022, Williams et al applied inverse weighted variance, Causal Analysis Using Summary Effect (CAUSE), and sensitivity analyses to evaluate risk factors for chronic back pain ( 30 ). Their study demonstrated that several life style factors including greater alcohol intake (inverse variance weighted OR = 1.29, 95% CI: 1.17–1.43, P = 7.2 × 10 −7 ) and smoking (inverse variance weighted OR = 1.27, 95% CI: 1.19–1.35, P = 7.0 × 10 −15 ) increased the risk of chronic back pain ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Dried fruit intake causally protects against low back pain: A Mendelian randomization study

Huang

Xie

2023

Front. Nutr.

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BackgroundLow back pain is the leading cause of years lived with disability worldwide. The aim of this study was to evaluate whether dried fruit intake causally protects against low back pain using two-sample Mendelian randomization (MR).MethodsWe obtained summary-level data for dried fruit intake (N = 421,764) from the IEU Open GWAS Project. Forty-one independent genetic variants proxied dried fruit intake. The corresponding data for low back pain were derived from the FinnGen project (13,178 cases and 164,682 controls; discovery data) and the Neale lab (5,423 cases and 355,771 controls; replication data). We conducted univariable and multivariable MR analyses.ResultsIn the univariable MR analysis, the inverse variance weighted estimate showed that greater dried fruit intake was associated with decreased risk of low back pain [odds ratio (OR) = 0.435, 95% confidence interval (CI): 0.287–0.659, P = 8.657 × 10−5]. Sensitivity analyses using the MR-Egger (OR = 0.078, 95% CI: 0.013–0.479, P = 0.009), maximum likelihood (OR = 0.433, 95% CI: 0.295–0.635, P = 1.801 × 10−5), weighted median (OR = 0.561, 95% CI: 0.325–0.967, P = 0.038) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) (OR = 0.454, 95% CI: 0.302–0.683, P = 4.535 × 10−4) methods showed consistent results. No evidence of directional pleiotropy was identified according to the Egger intercept (intercept P-value = 0.065) or applying the MR-PRESSO method (global test P-value = 0.164). The replication analysis yielded similar results. The multivariable MR revealed that the inverse association between dried fruit intake and low back pain was consistent after adjustment for fresh fruit intake, body mass index, current tobacco smoking, alcohol intake frequency, total body bone mineral density, serum 25-hydroxyvitamin D levels, and vigorous physical activity.ConclusionThis MR study provides evidence to support that dried fruit intake causally protects against low back pain.

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“…From a psychological perspective, both these conditions appear to be genetically linked to depression ( 14 ). Depressive disorders are more common in patients with these disorders than in the general population ( 27 , 28 ), and depression has been found to predict functional outcomes in these patients ( 29 , 30 ). Apart from depression, other negative emotional states such as anxiety and anger have also been associated with both the occurrence of these conditions, and the level of disability associated with them ( 31 – 33 ).…”

Section: Introductionmentioning

confidence: 99%

The influence of cultural and religious factors on cross-national variations in the prevalence of chronic back and neck pain: an analysis of data from the global burden of disease 2019 study

Rajkumar

2023

Front. Pain Res.

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IntroductionLow back pain and neck pain are among the most commonly reported forms of chronic pain worldwide, and are associated with significant distress, disability and impairment in quality of life. Though these categories of pain can be analyzed and treated from a biomedical perspective, there is evidence that they are both related to psychological variables such as depression and anxiety. The experience of pain can be significantly influenced by cultural values. For example, cultural beliefs and attitudes can influence the meaning attached to the experience of pain, the responses of others to a sufferer's pain, and the likelihood of seeking medical care for particular symptoms. Likewise, religious beliefs and practices can influence the both experience of pain and the responses to it. These factors have also been associated with variations in the severity of depression and anxiety.MethodsIn the current study, data on the estimated national prevalence of both low back pain and neck pain, obtained from the 2019 Global Burden of Disease Study (GBD 2019), is analyzed in relation to cross-national variations in cultural values, as measured using Hofstede's model (n =115 countries) and in religious belief and practice, based on the most recent Pew Research Center survey (n = 105 countries). To address possible confounding factors, these analyses were adjusted for variables known to be associated with chronic low back or neck pain, namely smoking, alcohol use, obesity, anxiety, depression and insufficient physical activity.ResultsIt was found that the cultural dimensions of Power Distance and Collectivism were inversely correlated with the prevalence of chronic low back pain, and Uncertainty Avoidance was inversely correlated with the prevalence of chronic neck pain, even after adjustment for potential confounders. Measures of religious affiliation and practice were negatively correlated with the prevalence of both conditions, but these associations were not significant after adjusting for cultural values and confounders.DiscussionThese results highlight the existence of meaningful cross-cultural variations in the occurrence of common forms of chronic musculoskeletal pain. Psychological and social factors that could account for these variations are reviewed, along with their implications for the holistic management of patients with these disorders.

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Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study

Cited by 18 publications

References 38 publications

A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra

A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra

Dried fruit intake causally protects against low back pain: A Mendelian randomization study

The influence of cultural and religious factors on cross-national variations in the prevalence of chronic back and neck pain: an analysis of data from the global burden of disease 2019 study

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