Genetic overlap between multi-site chronic pain and cognition: a large-scale genome-wide cross-trait analysis.

IF 3.2 3区医学 Q2 NEUROSCIENCES

Frontiers in Neuroscience Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.3389/fnins.2025.1466278

Yanjing Chen, Jiankai Deng, Zhiyi Zhang, Chenlin Wang, Xuegao Yu

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引用次数: 0

Abstract

Background: Different studies have consistently demonstrated a positive correlation between chronic pain and cognitive changes. This study aimed to explore the genetic factors underlying the relationship between chronic pain and cognitive traits, and to investigate whether an inherent causal connection exists between them.

Method: The genetic contributions of chronic multi-site pain and eight cognitive traits were investigated based on Genome-wide association studies (GWAS) data. Linkage disequilibrium score regression (LDSC) was employed to assess the genetic correlations between each pair of traits. The shared genetic components of these traits were investigated by identifying single nucleotide polymorphisms (SNPs) with pleiotropic effects using the Cross Phenotype Association (CPASSOC) method. Furthermore, enrichment analysis and transcriptome-wide association studies (TWAS) were performed to characterize the significant associations between genetic traits. The latent causal variable model (LCV) was employed to explore the potential causal relationship between both traits.

Results: A significant negative genetic correlation was found between chronic pain and several cognitive functions, particularly intelligence (rg = -0. 11, p = 7.77 × 10^-64). CPASSOC identified 150 pleiotropic loci. A co-localization analysis was conducted, which identified 20 loci exhibiting pleiotropic effects at the same genomic position. The LCV analysis indicated no causal relationship between both traits.

Conclusion: The present work contributed to an enhanced understanding of the complex genetic interplay between cognitive function and chronic pain.

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多位点慢性疼痛和认知之间的遗传重叠：一项大规模全基因组交叉性状分析。

背景：不同的研究一致表明慢性疼痛与认知变化之间存在正相关。本研究旨在探讨慢性疼痛与认知特征之间的遗传因素，并探讨两者之间是否存在内在的因果关系。方法：基于全基因组关联研究（Genome-wide association studies， GWAS）数据，研究慢性多位点疼痛和8种认知特征的遗传贡献。采用连锁不平衡评分回归（LDSC）评估各性状间的遗传相关性。利用交叉表型关联（Cross Phenotype Association， CPASSOC）方法鉴定具有多效效应的单核苷酸多态性（snp），研究了这些性状的共有遗传成分。此外，富集分析和转录组全关联研究（TWAS）来表征遗传性状之间的显著相关性。采用潜在因果变量模型（LCV）探讨两种性状之间的潜在因果关系。结果：慢性疼痛与几种认知功能，特别是智力之间存在显著的负相关遗传（rg = -0）。11, p = 7.77 × 10-64)。CPASSOC鉴定出150个多效位点。共定位分析发现，在同一基因组位置有20个基因座表现出多效性。LCV分析显示这两个性状之间没有因果关系。结论：本研究有助于进一步了解认知功能与慢性疼痛之间复杂的遗传相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Neuroscience NEUROSCIENCES-

CiteScore

6.20

自引率

4.70%

发文量

2070

审稿时长

14 weeks

期刊介绍： Neural Technology is devoted to the convergence between neurobiology and quantum-, nano- and micro-sciences. In our vision, this interdisciplinary approach should go beyond the technological development of sophisticated methods and should contribute in generating a genuine change in our discipline.