Candidate gene analysis of 535 "pain genes" and associations with reported intensity of chronic low back pain




Hurd, Christine A.
Lin, Emily
Broadbent, Dallen
Dubakula, Vishnu


0000-0002-2461-8521 (Hurd, Christine A.)

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Purpose: Numerous genome-wide association studies have been able to elucidate potential underlying genetic associations with clinical diagnoses. Chronic low back pain (CLBP) is a clinical presentation that has not yet been strongly associated with specific genetic markers. Several studies however have found genetic associations with other various pain disorders, such as the 535 genes identified by Ultsch et al. as "pain genes." Our group aims to find associations between previously identified pain-related genes and clinical reports of the intensity of low back pain using genetic and clinical data collected by the PRECISION Pain Research Registry. Methods: The PRECISION Pain Research Registry is a national registry that has collected demographic, clinical, and genetic information of patients with CLBP. Our analysis is querying associations between these identified "pain genes" and the intensity of low back pain reported by registry participants using a numerical rating scale (NRS). Methods: Participants in the PRECISION Pain Research Registry were genotyped via an Illumina iScan Array Scanner and Global Screening Array. The phenotype of CLBP will be measured by the NRS, which is an 11-point quantifier of pain intensity. The collected genotypes and phenotypic expression of pain will be compared via the Multi-marker Analysis of GenoMic Annotation (MAGMA), which enables candidate gene analysis of the 535 "pain genes" via congregation of single nucleotide polymorphisms (SNPs) and subsequent projection onto principal components in a matrix. Pain intensity will be evaluated as a function of genetic effects accounting for selected covariates-comorbid conditions with a documented relationship to CLBP, smoking status, and genetic ancestry plus residuals, with F-tests to determine the p-values of associations. Results: FN1 and STARD13 were found to be significantly associated with pain intensity in AA registry participants and VEGF-A was found to be significantly associated with widespread pain in NHW registry participants Conclusion: For treatment that is refractory to other strategies, targeted drugs for these protein products can be explored as treatments. These mentioned genes also have significant epigenetic regulation that could be explored in further studies.