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A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

ABSTRACT: BACKGROUND:Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. METHODS:A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5?M genetic variants across the genome, while adjusting for sex, age, education, and income. RESULTS:Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p < 5 × 10-8 for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. CONCLUSIONS:Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

SUBMITTER: Randall CL

PROVIDER: S-EPMC5494109 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

Randall Cameron L CL Wright Casey D CD Chernus Jonathan M JM McNeil Daniel W DW Feingold Eleanor E Crout Richard J RJ Neiswanger Katherine K Weyant Robert J RJ Shaffer John R JR Marazita Mary L ML

Pain research & management 20170615

<h4>Background</h4>Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain.<h4>Methods</h4>A genome-wide association study (GWAS; <i>N</i> = 990) was performed to identify plausible genes that may ...[more]

PMID: 28701861

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Project description:Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Dataset Information

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

Publications

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

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