A multi-trait approach identified seven novel genes for back pain-related phenotypes

Back pain (BP) is a major contributor to disability worldwide. We conducted a cross-sectional study analyzing three BP-related phenotypes: chronic BP (CBP), dorsalgia and intervertebral disc disorders (IDD), with heritability estimated at 40-60%. Less than half of the heritability is ex-plained by common genetic variants identified by GWAS. More powerful methods of statistical analysis may offer additional insight. Using imputed genotypes from the UK Biobank we per-formed a multi-trait gene-based association analysis of three BP-related phenotypes: CBP, dorsal-gia, and IDD. We identified and replicated 16 genes associated with BP-related traits. Seven of the detected genes, namely, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were previously unreported. Several new genes have been previously detected as associated with traits genetically correlated with BP or as included in pathways associated with BP. Our results verify the role of these genes in BP-related traits and provide new insights into the genetics of back pain. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work of Y.A.T., T.I.A., E.E.E., and N.M.B. was supported by the Russian Science Foundation (RSF) grant No. 22-15-20037 and the Government of the Novosibirsk region. ### 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: https://www.ukbiobank.ac.uk/ https://www.finngen.fi/ I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The results of the gene-based analysis are available in the ZENODO database: https://doi.org/10.5281/zenodo.8118630. The original data are available at: https://www.ukbiobank.ac.uk/ https://www.finngen.fi/