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. 2020 Jul 24;10(1):252.
doi: 10.1038/s41398-020-00941-z.

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Jie Sun  1   2   3 , Wei Yan  2 , Xing-Nan Zhang  2 , Xiao Lin  2 , Hui Li  2 , Yi-Miao Gong  2 , Xi-Mei Zhu  2 , Yong-Bo Zheng  2 , Xiang-Yang Guo  3 , Yun-Dong Ma  2 , Zeng-Yi Liu  2 , Lin Liu  2 , Jia-Hong Gao  4 , Michael V Vitiello  5 , Su-Hua Chang  6   7 , Xiao-Guang Liu  8   9 , Lin Lu  10   11
Affiliations

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Jie Sun et al. Transl Psychiatry. .

Abstract

Chronic pain and sleep disturbance are highly comorbid disorders, which leads to barriers to treatment and significant healthcare costs. Understanding the underlying genetic and neural mechanisms of the interplay between sleep disturbance and chronic pain is likely to lead to better treatment. In this study, we combined 1206 participants with phenotype data, resting-state functional magnetic resonance imaging (rfMRI) data and genotype data from the Human Connectome Project and two large sample size genome-wide association studies (GWASs) summary data from published studies to identify the genetic and neural bases for the association between pain and sleep disturbance. Pittsburgh sleep quality index (PSQI) score was used for sleep disturbance, pain intensity was measured by Pain Intensity Survey. The result showed chronic pain was significantly correlated with sleep disturbance (r = 0.171, p-value < 0.001). Their genetic correlation was rg = 0.598 using linkage disequilibrium (LD) score regression analysis. Polygenic score (PGS) association analysis showed PGS of chronic pain was significantly associated with sleep and vice versa. Nine shared functional connectivity (FCs) were identified involving prefrontal cortex, temporal cortex, precentral/postcentral cortex, anterior cingulate cortex, fusiform gyrus and hippocampus. All these FCs mediated the effect of sleep disturbance on pain and seven FCs mediated the effect of pain on sleep disturbance. The chronic pain PGS was positively associated with the FC between middle temporal gyrus and hippocampus, which further mediated the effect of chronic pain PGS on PSQI score. Mendelian randomization analysis implied a possible causal relationship from chronic pain to sleep disturbance was stronger than that of sleep disturbance to chronic pain. The results provided genetic and neural evidence for the association between pain and sleep disturbance, which may inform future treatment approaches for comorbid chronic pain states and sleep disturbance.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Flowchart of analyses.
The analyses that were performed in this study included (1) phenotypic correlation, (2) genetic correlation using LD score regression and polygenic score (PGS) association analysis, (3) shared brain functional connectivity (FC) using network-based statistics method by analyzing rfMRI data, (4) association of the PGS with shared brain functional connectivity, and (5) causal relationship inference using Mendelian randomization (MR). HCP (Human Connectome Project) is the data source. N is the sample size for the analysis.
Fig. 2
Fig. 2. Chronic pain and sleep disturbance shared functional connectivities (FC) and the mediation function of the FC on the association between two phenotypes and the association between polygenic score and phenotypes.
a Area with the nine FCs shared by PSQI and CPb, color is proportional to the links connected with the node. b Nine significant FCs with nodes and edges indicated, node size is proportional to the links connected with the node. c Mediation model for the mediation of the FC (“right middle temporal gyrus” - “right hippocampus”) for the correlation between PSQI and CPb. The mediation model for eight other significant FCs are shown in Supplementary Table 2. d Association results of PGS of chronic pain with FC (“right middle temporal gyrus” - “right hippocampus”) and mediation model for the indirect effect of PGS of chronic pain (CP) on PSQI through FC (“right middle temporal gyrus” - “right hippocampus”). SFGdor: superior frontal gyrus, dorsolateral; MFG: middle frontal gyrus; MTG: middle temporal gyrus; ITG: inferior temporal gyrus; ACC&PaCG: anterior cingulate & paracingulate gyri; HIP: hippocampus; FFG: fusiform gyrus; IFGtriang: interior frontal gyrus, triangular part; PreCG: precentral gyrus; PoCG: postcentral gyrus. For mediation model, X is independent variable, Y is outcome variable, M is mediation variable. Path a is the effect of X on M, path b is the effect of M on Y, path c is the effect of X on Y (total effect), c’ is the indirect effect of X on Y. PSQI: Pittsburgh sleep quality index; CP: chronic pain; CPb: chronic pain binary; PGS: polygenic score; #SNP: number of SNPs used to calculate PGS; P-th: p-value threshold to define SNPs with P < P-th to calculate the PGS.
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References

    1. Afolalu EF, Ramlee F, Tang NKY. Effects of sleep changes on pain-related health outcomes in the general population: a systematic review of longitudinal studies with exploratory meta-analysis. Sleep. Med Rev. 2018;39:82–97. - PMC - PubMed
    1. Roy M, Piche M, Chen JI, Peretz I, Rainville P. Cerebral and spinal modulation of pain by emotions. Proc. Natl. Acad. Sci. USA. 2009;106:20900–20905. - PMC - PubMed
    1. Disease GBD, Injury I. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–1858. - PMC - PubMed
    1. Roenneberg T. Chronobiology: the human sleep project. Nature. 2013;498:427–428. - PubMed
    1. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J. Pain. 2013;14:1539–1552. - PMC - PubMed

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