Genome-wide analysis identifies significant contribution of brain-expressed genes in chronic, but not acute, back pain

Back pain is the leading cause of disability worldwide. Although most cases of back pain are acute, 20% of people with acute back pain go on to experience chronic back pain symptoms. It is unclear if acute and chronic pain states have similar or distinct underlying genetic mechanisms. Here we performed a genome-wide analysis for acute and chronic back pain in 375,158 individuals and found a significant genetic contribution to chronic, but not to acute, back pain. Using the UK Biobank cohort for discovery and the HUNT cohort for replication, we identified 7 loci for chronic back pain, of which 3 are novel. Pathway analyses, tissue-specific heritability enrichment analyses, epigenetic characterization, and tissue-specific transcriptome mapping in mouse pain models suggest a substantial genetic contribution to chronic, but not acute, back pain from the loci predominantly expressed in the central nervous system. Our findings show that chronic back pain is more heritable than acute back pain and is driven mostly by genes expressed in the central nervous system. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding for this work was kindly provided by the Canadian Excellence Research Chairs (CERC) Program ([www.cerc.gc.ca][1]) grant CERC09 (to LD). DVZ was supported in part by the Intramural Research Program of the NIH. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank has obtained Research Tissue Bank (RTB) approval from its ethics committee. The Norwegian Data Inspectorate has licensed HUNT Research Centre to store and link data collected in all HUNT surveys. All HUNT surveys, and the present nonparticipant study, are approved by The Regional Committee for Medical and Health Research Ethics. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets used in this work can be downloaded from the following sources. [http://download.baderlab.org/EM\_Genesets/December\_01_2019/][2] [1]: http://www.cerc.gc.ca [2]: http://download.baderlab.org/EM_Genesets/December_01_2019/